{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T04:41:17Z","timestamp":1760244077085,"version":"build-2065373602"},"reference-count":295,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2009,12,23]],"date-time":"2009-12-23T00:00:00Z","timestamp":1261526400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Insulin, besides its glucose lowering effects, is involved in the modulation of lifespan, aging and memory and learning processes. As the population ages, neurodegenerative disorders become epidemic and a connection between insulin signaling dysregulation, cognitive decline and dementia has been established. Mitochondria are intracellular organelles that despite playing a critical role in cellular metabolism are also one of the major sources of reactive oxygen species. Mitochondrial dysfunction, oxidative stress and neuroinflammation, hallmarks of neurodegeneration, can result from impaired insulin signaling. Insulin-sensitizing drugs such as the thiazolidinediones are a new class of synthetic compounds that potentiate insulin action in the target tissues and act as specific agonists of the peroxisome proliferator-activated receptor gamma (PPAR-\u03b3). Recently, several PPAR agonists have been proposed as novel and possible therapeutic agents for neurodegenerative disorders. Indeed, the literature shows that these agents are able to protect against mitochondrial dysfunction, oxidative damage, inflammation and apoptosis. This review discusses the role of mitochondria and insulin signaling in normal brain function and in neurodegeneration. Furthermore, the potential protective role of insulin and insulin sensitizers in Alzheimer\u00b4s, Parkinson\u00b4s and Huntington\u00b4s diseases and amyotrophic lateral sclerosis will be also discussed.<\/jats:p>","DOI":"10.3390\/ph2030250","type":"journal-article","created":{"date-parts":[[2009,12,25]],"date-time":"2009-12-25T04:53:37Z","timestamp":1261716817000},"page":"250-286","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Insulin and Insulin-Sensitizing Drugs in Neurodegeneration: Mitochondria as Therapeutic Targets"],"prefix":"10.3390","volume":"2","author":[{"given":"Susana","family":"Cardoso","sequence":"first","affiliation":[{"name":"Center for Neuroscience and Cell Biology, University of Coimbra, 3000-354 Coimbra, Portugal"},{"name":"Department of Life Sciences, Faculty of Sciences and Technology, University of Coimbra, 3000- 354 Coimbra, Portugal"}]},{"given":"Renato","family":"Santos","sequence":"additional","affiliation":[{"name":"Center for Neuroscience and Cell Biology, University of Coimbra, 3000-354 Coimbra, Portugal"},{"name":"Department of Life Sciences, Faculty of Sciences and Technology, University of Coimbra, 3000- 354 Coimbra, Portugal"}]},{"given":"Sonia","family":"Correia","sequence":"additional","affiliation":[{"name":"Center for Neuroscience and Cell Biology, University of Coimbra, 3000-354 Coimbra, Portugal"},{"name":"Department of Life Sciences, Faculty of Sciences and Technology, University of Coimbra, 3000- 354 Coimbra, Portugal"}]},{"given":"Cristina","family":"Carvalho","sequence":"additional","affiliation":[{"name":"Center for Neuroscience and Cell Biology, University of Coimbra, 3000-354 Coimbra, Portugal"},{"name":"Department of Life Sciences, Faculty of Sciences and Technology, University of Coimbra, 3000- 354 Coimbra, Portugal"}]},{"given":"Xiongwei","family":"Zhu","sequence":"additional","affiliation":[{"name":"School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA"}]},{"given":"Hyoung-Gon","family":"Lee","sequence":"additional","affiliation":[{"name":"School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA"}]},{"given":"Gemma","family":"Casadesus","sequence":"additional","affiliation":[{"name":"School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA"}]},{"given":"Mark  A.","family":"Smith","sequence":"additional","affiliation":[{"name":"School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA"}]},{"given":"George","family":"Perry","sequence":"additional","affiliation":[{"name":"College of Sciences, The University of Texas at San Antonio, TX 78249, USA"}]},{"given":"Paula  I.","family":"Moreira","sequence":"additional","affiliation":[{"name":"Center for Neuroscience and Cell Biology, University of Coimbra, 3000-354 Coimbra, Portugal"},{"name":"Institute of Physiology, Faculty of Medicine, University of Coimbra, 3000-354 Coimbra, Portugal"}]}],"member":"1968","published-online":{"date-parts":[[2009,12,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.pneurobio.2006.06.003","article-title":"Insulin signaling in the central nervous system: Learning to survive","volume":"79","author":"Ramakers","year":"2006","journal-title":"Prog. Neurobiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0021-9258(17)42297-6","article-title":"The insulin signaling system","volume":"269","author":"White","year":"1994","journal-title":"J. Biol. Chem."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1146\/annurev.physiol.70.113006.100533","article-title":"Insulin-like signaling, nutrient homeostasis, and life span","volume":"70","author":"Taguchi","year":"2008","journal-title":"Annu. Rev. Physiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1038\/366461a0","article-title":"A C. elegans mutant that lives twice as long as wild type","volume":"366","author":"Kenyon","year":"1993","journal-title":"Nature"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1126\/science.1098219","article-title":"Long-lived drosophila With overexpressed dFOXO in adult fat body","volume":"305","author":"Giannakou","year":"2004","journal-title":"Science"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/j.mad.2004.03.006","article-title":"The paradox of the insulin\/IGF-1 signaling pathway in longevity","volume":"125","author":"Rincon","year":"2004","journal-title":"Mech. Ageing Dev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1038\/nrn2474","article-title":"The insulin paradox: Aging, proteotoxicity and neurodegeneration","volume":"10","author":"Cohen","year":"2008","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1101\/lm.88005","article-title":"Insulin receptor signaling in long-term memory consolidation following spatial learning","volume":"12","author":"Dou","year":"2005","journal-title":"Learn. Mem."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1016\/j.neuroscience.2006.02.084","article-title":"Insulin-like growth factor I interfaces with brain-derived neurotrophic factor-mediated synaptic plasticity to modulate aspects of exercise-induced cognitive function","volume":"140","author":"Ding","year":"2006","journal-title":"Neuroscience"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/0197-4580(95)02002-0","article-title":"Memory improvement following induced hyperinsulinemia in Alzheimer's disease","volume":"17","author":"Craft","year":"1996","journal-title":"Neurobiol. Aging"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1016\/S0166-2236(03)00163-2","article-title":"Potential roles of insulin and IGF-1 in Alzheimer's disease","volume":"26","author":"Gasparini","year":"2003","journal-title":"Trends Neurosci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"27","DOI":"10.2165\/00023210-200317010-00003","article-title":"The role of insulin resistance in the pathogenesis of Alzheimer's disease: Implications for treatment","volume":"17","author":"Watson","year":"2003","journal-title":"CNS Drugs"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1016\/0024-3205(95)00055-B","article-title":"Bioenergetic and oxidative stress in neurodegenerative diseases","volume":"56","author":"Bowling","year":"1995","journal-title":"Life Sci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.neurobiolaging.2005.08.014","article-title":"The impact of recurrent hypoglycemia on cognitive function in aging","volume":"26","author":"McNay","year":"2005","journal-title":"Neurobiol. Aging"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Moreira, P.I., Duarte, A.I., Santos, M.S., Rego, A.C., and Oliveira, C.R. (2009). An integrative view of the role of oxidative stress, mitochondria and insulin in Alzheimer's disease. J. Alzheimers Dis., 741\u2013761.","DOI":"10.3233\/JAD-2009-0972"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"324","DOI":"10.1016\/j.tem.2008.08.001","article-title":"Is mitochondrial dysfunction a cause of insulin resistance?","volume":"19","author":"Turner","year":"2008","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1002\/ana.20624","article-title":"Mitochondria take center stage in aging and neurodegeneration","volume":"58","author":"Beal","year":"2005","journal-title":"Ann. Neurol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1621","DOI":"10.1089\/ars.2007.1703","article-title":"Alzheimer's disease: A lesson from mitochondrial dysfunction","volume":"9","author":"Moreira","year":"2007","journal-title":"Antioxid. Redox Signal"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.arr.2008.01.001","article-title":"Molecular mechanism of PPAR in the regulation of age-related inflammation","volume":"7","author":"Chung","year":"2008","journal-title":"Ageing Res. Rev."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1111\/j.1471-4159.2008.05388.x","article-title":"PPAR: A therapeutic target in Parkinson's disease","volume":"106","author":"Chaturvedi","year":"2008","journal-title":"J. Neurochem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1097\/00041433-200310000-00006","article-title":"Peroxisome proliferator-activated receptors: New targets for the pharmacological modulation of macrophage gene expression and function","volume":"14","author":"Chinetti","year":"2003","journal-title":"Curr. Opin. Lipidol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.tips.2004.03.012","article-title":"Peroxisome proliferator-activated receptor gamma in diabetes and metabolism","volume":"25","author":"Rangwala","year":"2004","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_23","first-page":"1045","article-title":"Peroxisome proliferator activated receptor ligands for the treatment of insulin resistance","volume":"5","author":"Patsouris","year":"2004","journal-title":"Curr. Opin. Investig. Drugs"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.neuint.2006.03.020","article-title":"PPARgamma as a therapeutic target in central nervous system diseases","volume":"49","author":"Sundararajan","year":"2006","journal-title":"Neurochem. Int."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1016\/j.nurt.2008.05.003","article-title":"PPARgamma agonists as therapeutics for the treatment of Alzheimer's disease","volume":"5","author":"Landreth","year":"2008","journal-title":"Neurotherapeutics"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1038\/sj.tpj.6500397","article-title":"Complex disease-associated pharmacogenetics: Drug efficacy, drug safety, and confirmation of a pathogenetic hypothesis (Alzheimer's disease)","volume":"7","author":"Roses","year":"2007","journal-title":"Pharmacogenomics J."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/j.tins.2008.02.008","article-title":"The mitochondrial impairment, oxidative stress and neurodegeneration connection: Reality or just an attractive hypothesis?","volume":"31","author":"Fukui","year":"2008","journal-title":"Trends Neurosci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1038\/sj.cdd.4402160","article-title":"Mitochondrial dysfunction in Parkinson's disease","volume":"14","author":"Schapira","year":"2007","journal-title":"Cell Death Differ."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1172\/JCI200317741","article-title":"Neuronal degeneration and mitochondrial dysfunction","volume":"111","author":"Schon","year":"2003","journal-title":"J Clin Invest"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"59","DOI":"10.3233\/JAD-2006-10110","article-title":"Mitochondrial dysfunction, oxidative stress and neurodegeneration","volume":"10","author":"Mancuso","year":"2006","journal-title":"J. Alzheimers Dis."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1016\/j.biocel.2006.07.001","article-title":"Free radicals and antioxidants in normal physiological functions and human disease","volume":"39","author":"Valko","year":"2007","journal-title":"Int J. Biochem. Cell Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"369","DOI":"10.2741\/999","article-title":"Mitogen-activated protein kinase pathways in redox signaling","volume":"8","author":"Torres","year":"2003","journal-title":"Front Biosci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2896","DOI":"10.1016\/S0021-9258(19)39885-0","article-title":"The insulin mimetic agents H2O2 and vanadate stimulate protein tyrosine phosphorylation in intact cells","volume":"265","author":"Heffetz","year":"1990","journal-title":"J. Biol. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1016\/S0014-5793(97)00541-3","article-title":"Activation of protein kinase B (Akt\/RAC-protein kinase) by cellular stress and its association with heat shock protein Hsp27","volume":"410","author":"Konishi","year":"1997","journal-title":"FEBS Lett."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"23357","DOI":"10.1074\/jbc.M100320200","article-title":"Modulation of mitochondrial function by hydrogen peroxide","volume":"276","author":"Nulton","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"13245","DOI":"10.1074\/jbc.273.21.13245","article-title":"Overexpression of manganese superoxide dismutase suppresses tumor necrosis factor-induced apoptosis and activation of nuclear transcription factor-kappaB and activated protein-1","volume":"273","author":"Manna","year":"1998","journal-title":"J. Biol. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1475","DOI":"10.1016\/S0891-5849(02)01113-9","article-title":"Is oxidative damage the fundamental pathogenic mechanism of Alzheimer\u2019s and other neurodegenerative diseases?","volume":"33","author":"Perry","year":"2002","journal-title":"Free Radic. Biol. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1093\/geronj\/11.3.298","article-title":"Aging: A theory based on free radical and radiation chemistry","volume":"11","author":"Harman","year":"1956","journal-title":"J. Gerontol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1021\/tx700210j","article-title":"Oxidative stress and neurotoxicity","volume":"21","author":"Sayre","year":"2008","journal-title":"Chem. Res. Toxicol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1038\/nature05292","article-title":"Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases","volume":"443","author":"Lin","year":"2006","journal-title":"Nature"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.exger.2007.10.001","article-title":"The role of mitochondrial DNA mutations in aging and sarcopenia: Implications for the mitochondrial vicious cycle theory of aging","volume":"43","author":"Hiona","year":"2008","journal-title":"Exp. Gerontol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"3238","DOI":"10.1093\/nar\/gkm215","article-title":"Expression of catalytic mutants of the mtDNA helicase Twinkle and polymerase POLG causes distinct replication stalling phenotypes","volume":"35","author":"Wanrooij","year":"2007","journal-title":"Nucleic Acids Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1016\/j.exger.2006.06.056","article-title":"Mitochondrial respiration and reactive oxygen species in C. elegans","volume":"41","author":"Sedensky","year":"2006","journal-title":"Exp. Gerontol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1016\/S1534-5807(01)00071-5","article-title":"Mitochondrial electron transport is a key determinant of life span in Caenorhabditis elegans","volume":"1","author":"Feng","year":"2001","journal-title":"Dev. Cell"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2398","DOI":"10.1126\/science.1077780","article-title":"Rates of behavior and aging specified by mitochondrial function during development","volume":"298","author":"Dillin","year":"2002","journal-title":"Science"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"169","DOI":"10.3233\/JAD-2002-4307","article-title":"Non-familial Alzheimer's disease is mainly due to genetic factors","volume":"4","author":"Ashford","year":"2002","journal-title":"J. Alzheimers Dis."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1007\/s10540-007-9038-z","article-title":"Mitochondria and neurodegeneration","volume":"27","author":"Petrozzi","year":"2007","journal-title":"Biosci. Rep."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1196\/annals.1427.027","article-title":"Mitochondrial approaches for neuroprotection","volume":"1147","author":"Chaturvedi","year":"2008","journal-title":"Ann. NY Acad. Sci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.molmed.2007.12.002","article-title":"Amyloid beta, mitochondrial dysfunction and synaptic damage: Implications for cognitive decline in aging and Alzheimer's disease","volume":"14","author":"Reddy","year":"2008","journal-title":"Trends Mol. Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1080\/13813450701572288","article-title":"Effects of Alzheimer's amyloid-beta and tau protein on mitochondrial function\u2014Role of glucose metabolism and insulin signalling","volume":"113","author":"Rhein","year":"2007","journal-title":"Arch. Physiol. Biochem."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"101","DOI":"10.3233\/JAD-2006-9202","article-title":"The key role of mitochondria in Alzheimer's disease","volume":"9","author":"Moreira","year":"2006","journal-title":"J. Alzheimers. Dis."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"492","DOI":"10.2174\/187152709789824651","article-title":"Mitochondria as a Therapeutic Target in Alzheimer's Disease and Diabetes","volume":"8","author":"Moreira","year":"2009","journal-title":"CNS Neurol. Disord. Drug Targets."},{"key":"ref_53","first-page":"823","article-title":"Intra- and extracellular Abeta and PHF in clinically evaluated cases of Alzheimer\u2019s disease","volume":"19","author":"Fernandez","year":"2004","journal-title":"Histol. Histopathol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1439","DOI":"10.1096\/fj.00-0561fje","article-title":"Functional mitochondria are required for amyloid beta-mediated neurotoxicity","volume":"15","author":"Cardoso","year":"2001","journal-title":"FASEB J."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"789","DOI":"10.1023\/A:1015536808304","article-title":"Amyloid beta-peptide promotes permeability transition pore in brain mitochondria","volume":"21","author":"Moreira","year":"2001","journal-title":"Biosci. Rep."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1002\/jnr.10282","article-title":"Effect of amyloid beta-peptide on permeability transition pore: A comparative study","volume":"69","author":"Moreira","year":"2002","journal-title":"J Neurosci. Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1449","DOI":"10.2337\/diabetes.52.6.1449","article-title":"Increased vulnerability of brain mitochondria in diabetic (Goto-Kakizaki) rats with aging and amyloid-beta exposure","volume":"52","author":"Moreira","year":"2003","journal-title":"Diabetes"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1126\/science.1091230","article-title":"ABAD directly links Abeta to mitochondrial toxicity in Alzheimer's disease","volume":"304","author":"Lustbader","year":"2004","journal-title":"Science"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1093\/jnen\/60.8.759","article-title":"Oxidative damage is the earliest event in Alzheimer disease","volume":"60","author":"Nunomura","year":"2001","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"4183","DOI":"10.1523\/JNEUROSCI.21-12-04183.2001","article-title":"Increased lipid peroxidation precedes amyloid plaque formation in an animal model of Alzheimer amyloidosis","volume":"21","author":"Uryu","year":"2001","journal-title":"J. Neurosci."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1225","DOI":"10.1093\/hmg\/ddh140","article-title":"Gene expression profiles of transcripts in amyloid precursor protein transgenic mice: Up-regulation of mitochondrial metabolism and apoptotic genes is an early cellular change in Alzheimer's disease","volume":"13","author":"Reddy","year":"2004","journal-title":"Hum. Mol. Genet."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1083\/jcb.200108057","article-title":"Tau blocks traffic of organelles, neurofilaments, and APP vesicles in neurons and enhances oxidative stress","volume":"156","author":"Stamer","year":"2002","journal-title":"J. Cell Biol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"23802","DOI":"10.1074\/jbc.M500356200","article-title":"Proteomic and functional analyses reveal a mitochondrial dysfunction in P301L tau transgenic mice","volume":"280","author":"David","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1104","DOI":"10.1007\/s00259-003-1194-1","article-title":"Cerebral metabolic changes accompanying conversion of mild cognitive impairment into Alzheimer's disease: A PET follow-up study","volume":"30","author":"Drzezga","year":"2003","journal-title":"Eur. J. Nucl. Med. Mol. Imaging"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1176\/appi.ajp.159.5.738","article-title":"Longitudinal PET Evaluation of Cerebral Metabolic Decline in Dementia: A Potential Outcome Measure in Alzheimer's Disease Treatment Studies","volume":"159","author":"Alexander","year":"2002","journal-title":"Am. J. Psychiatry"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1002\/ana.20474","article-title":"Mitochondrial abnormalities in Alzheimer brain: Mechanistic implications","volume":"57","author":"Bubber","year":"2005","journal-title":"Ann. Neurol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/S0925-4439(02)00222-3","article-title":"Inhibition of the alpha-ketoglutarate dehydrogenase complex alters mitochondrial function and cellular calcium regulation","volume":"1637","author":"Huang","year":"2003","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1002\/1531-8249(200009)48:3<297::AID-ANA3>3.0.CO;2-Z","article-title":"Mitochondrial damage in Alzheimer's disease varies with apolipoprotein E genotype","volume":"48","author":"Gibson","year":"2000","journal-title":"Ann. Neurol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1016\/0278-5846(86)90029-1","article-title":"Energy metabolism in demented brain","volume":"10","author":"Sorbi","year":"1986","journal-title":"Prog. Neuropsychopharmacol. Biol. Psychiatry."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"195","DOI":"10.3233\/JAD-2007-12210","article-title":"Lipoic acid and N-acetyl cysteine decrease mitochondrial-related oxidative stress in Alzheimer disease patient fibroblasts","volume":"12","author":"Moreira","year":"2007","journal-title":"J. Alzheimers Dis."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/S0014-5793(99)01028-5","article-title":"Beta-Amyloid fragment 25-35 selectively decreases complex IV activity in isolated mitochondria","volume":"457","author":"Canevari","year":"1999","journal-title":"FEBS Lett."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1437","DOI":"10.1093\/hmg\/ddl066","article-title":"Mitochondria are a direct site of A beta accumulation in Alzheimer's disease neurons: Implications for free radical generation and oxidative damage in disease progression","volume":"15","author":"Manczak","year":"2006","journal-title":"Hum. Mol. Genet."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1016\/S0197-4580(00)00234-7","article-title":"Cytochrome c oxidase deficient cells accumulate in the hippocampus and choroid plexus with age","volume":"22","author":"Cottrell","year":"2001","journal-title":"Neurobiol. Aging"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/S0169-328X(96)00191-X","article-title":"Decreased expression of nuclear and mitochondrial DNA-encoded genes of oxidative phosphorylation in association neocortex in Alzheimer disease","volume":"44","author":"Chandrasekaran","year":"1997","journal-title":"Brain Res. Mol. Brain Res."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1302","DOI":"10.1212\/WNL.40.8.1302","article-title":"Cytochrome oxidase deficiency in Alzheimer's disease","volume":"40","author":"Parker","year":"1990","journal-title":"Neurology"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1016\/S0304-3940(97)00741-6","article-title":"Oxidative metabolism in cultured fibroblasts derived from sporadic Alzheimer's disease (AD) patients","volume":"236","author":"Curti","year":"1997","journal-title":"Neurosci. Lett."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/j.mito.2006.10.004","article-title":"Impaired platelet mitochondrial activity in Alzheimer's disease and mild cognitive impairment","volume":"6","author":"Valla","year":"2006","journal-title":"Mitochondrion"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1126\/science.2814477","article-title":"Human cells lacking mtDNA: Repopulation with exogenous mitochondria by complementation","volume":"246","author":"King","year":"1989","journal-title":"Science"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1212\/WNL.49.4.918","article-title":"Cybrids in Alzheimer's disease: A cellular model of the disease?","volume":"49","author":"Swerdlow","year":"1997","journal-title":"Neurology"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.nbd.2003.09.011","article-title":"Mitochondrial abnormalities in cybrid cell models of sporadic Alzheimer's disease worsen with passage in culture","volume":"15","author":"Trimmer","year":"2004","journal-title":"Neurobiol. Dis."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1111\/j.1471-4159.2004.02438.x","article-title":"Mitochondria dysfunction of Alzheimer's disease cybrids enhances Abeta toxicity","volume":"89","author":"Cardoso","year":"2004","journal-title":"J. Neurochem."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1093\/hmg\/11.2.133","article-title":"High aggregate burden of somatic mtDNA point mutations in aging and Alzheimer's disease brain","volume":"11","author":"Lin","year":"2002","journal-title":"Hum. Mol. Genet."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1016\/j.expneurol.2009.01.011","article-title":"The Alzheimer's disease mitochondrial cascade hypothesis: An update","volume":"218","author":"Swerdlow","year":"2009","journal-title":"Exp. Neurol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"564","DOI":"10.1002\/ana.20417","article-title":"Mitochondrial DNA haplogroup cluster UKJT reduces the risk of PD","volume":"57","author":"Pyle","year":"2005","journal-title":"Ann. Neurol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1212\/WNL.47.1.254","article-title":"Increased risk of dementia in mothers of Alzheimer's disease cases: Evidence for maternal inheritance","volume":"47","author":"Edland","year":"1996","journal-title":"Neurology"},{"key":"ref_86","unstructured":"Wolf, P.A., Beiser, A., Au, R., Auerbach, S., and DeCarli, C. (2005). Neurology, 64, 267\u2013268."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"4526","DOI":"10.1073\/pnas.94.9.4526","article-title":"Mutations in mitochondrial cytochrome c oxidase genes segregate with late-onset Alzheimer disease","volume":"94","author":"Davis","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1007\/s00439-005-0123-8","article-title":"Does the mitochondrial genome play a role in the etiology of Alzheimer's disease?","volume":"119","author":"Elson","year":"2006","journal-title":"Hum. Genet."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"167","DOI":"10.3233\/JAD-2006-9209","article-title":"Molecular indices of oxidative stress and mitochondrial dysfunction occur early and often progress with severity of Alzheimer's disease","volume":"9","author":"Wands","year":"2006","journal-title":"J. Alzheimers Dis."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"3017","DOI":"10.1523\/JNEUROSCI.21-09-03017.2001","article-title":"Mitochondrial abnormalities in Alzheimer's disease","volume":"21","author":"Hirai","year":"2001","journal-title":"J. Neurosci."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1097\/01.jnen.0000240476.73532.b0","article-title":"Autophagocytosis of mitochondria is prominent in Alzheimer disease","volume":"66","author":"Moreira","year":"2007","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"614","DOI":"10.4161\/auto.4872","article-title":"Increased autophagic degradation of mitochondria in Alzheimer disease","volume":"3","author":"Moreira","year":"2007","journal-title":"Autophagy"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"14163","DOI":"10.1073\/pnas.0705738104","article-title":"Cytochrome c oxidase deficiency in neurons decreases both oxidative stress and amyloid formation in a mouse model of Alzheimer's disease","volume":"104","author":"Fukui","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1126\/science.6823561","article-title":"Chronic Parkinsonism in humans due to a product of meperidine-analog synthesis","volume":"219","author":"Langston","year":"1983","journal-title":"Science"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1038\/81834","article-title":"Chronic systemic pesticide exposure reproduces features of Parkinson's disease","volume":"3","author":"Betarbet","year":"2000","journal-title":"Nat. Neurosci."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"42026","DOI":"10.1074\/jbc.M508628200","article-title":"Rotenone model of Parkinson disease: Multiple brain mitochondria dysfunctions after short term systemic rotenone intoxication","volume":"280","author":"Panov","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1002\/ana.410440207","article-title":"Mitochondrial DNA transmission of the mitochondrial defect in Parkinson's disease","volume":"44","author":"Gu","year":"1998","journal-title":"Ann. Neurol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/j.mito.2008.03.004","article-title":"Mitochondrial function in Parkinson's disease cybrids containing an nt2 neuron-like nuclear background","volume":"8","author":"Esteves","year":"2008","journal-title":"Mitochondrion"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.1126\/science.1096284","article-title":"Hereditary early-onset Parkinson's disease caused by mutations in PINK1","volume":"304","author":"Valente","year":"2004","journal-title":"Science"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"11364","DOI":"10.1073\/pnas.0802076105","article-title":"Loss of PINK1 causes mitochondrial functional defects and increased sensitivity to oxidative stress","volume":"105","author":"Gautier","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_101","first-page":"1","article-title":"PINK1 defect causes mitochondrial dysfunction, proteasomal deficit and alpha-synuclein aggregation in cell culture models of Parkinson's disease","volume":"4","author":"Liu","year":"2009","journal-title":"PLoS One"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.neulet.2005.07.045","article-title":"Analysis of LRRK 2 G 2019 S and I 2020 T mutations in Parkinson's disease","volume":"390","author":"Bialecka","year":"2005","journal-title":"Neurosci. Lett."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.neulet.2005.07.044","article-title":"The dardarin G 2019 S mutation is a common cause of Parkinson's disease but not other neurodegenerative diseases","volume":"389","author":"Hernandez","year":"2005","journal-title":"Neurosci. Lett."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1038\/cdd.2008.166","article-title":"Mitochondrial dysfunction triggered by loss of HtrA2 results in the activation of a brain-specific transcriptional stress response","volume":"16","author":"Moisoi","year":"2009","journal-title":"Cell Death Differ."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"2099","DOI":"10.1093\/hmg\/ddi215","article-title":"Loss of function mutations in the gene encoding Omi\/HtrA2 in Parkinson's disease","volume":"14","author":"Strauss","year":"2005","journal-title":"Hum. Mol. Genet."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/S0014-4886(03)00342-X","article-title":"Enhanced substantia nigra mitochondrial pathology in human alpha-synuclein transgenic mice after treatment with MPTP","volume":"186","author":"Song","year":"2004","journal-title":"Exp. Neurol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/S0002-9440(10)64553-1","article-title":"Alpha-synuclein promotes mitochondrial deficit and oxidative stress","volume":"157","author":"Hsu","year":"2000","journal-title":"Am. J. Pathol."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"9089","DOI":"10.1074\/jbc.M710012200","article-title":"Mitochondrial import and accumulation of alpha-synuclein impair complex I in human dopaminergic neuronal cultures and Parkinson disease brain","volume":"283","author":"Devi","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"14524","DOI":"10.1073\/pnas.172514599","article-title":"Resistance of alpha-synuclein null mice to the parkinsonian neurotoxin MPTP","volume":"99","author":"Dauer","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1016\/j.nbd.2005.08.018","article-title":"Mice lacking alpha-synuclein are resistant to mitochondrial toxins","volume":"21","author":"Klivenyi","year":"2006","journal-title":"Neurobiol. Dis."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1093\/hmg\/ddg044","article-title":"Parkin prevents mitochondrial swelling and cytochrome c release in mitochondria-dependent cell death","volume":"12","author":"Darios","year":"2003","journal-title":"Hum. Mol. Genet"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"18614","DOI":"10.1074\/jbc.M401135200","article-title":"Mitochondrial dysfunction and oxidative damage in parkin-deficient mice","volume":"279","author":"Palacino","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1093\/hmg\/ddl006","article-title":"Parkin enhances mitochondrial biogenesis in proliferating cells","volume":"15","author":"Kuroda","year":"2006","journal-title":"Hum. Mol. Genet."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1007\/s00415-003-1304-9","article-title":"New insights into Parkinson's disease","volume":"250","author":"Chung","year":"2003","journal-title":"J. Neurol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"8024","DOI":"10.1073\/pnas.0501078102","article-title":"Increased glutathione S-transferase activity rescues dopaminergic neuron loss in a Drosophila model of Parkinson's disease","volume":"102","author":"Whitworth","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"2063","DOI":"10.1093\/hmg\/ddi211","article-title":"Mitochondrial localization of the Parkinson's disease related protein DJ-1: Implications for pathogenesis","volume":"14","author":"Zhang","year":"2005","journal-title":"Hum. Mol. Genet."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1016\/j.bbrc.2004.05.187","article-title":"Reduced anti-oxidative stress activities of DJ-1 mutants found in Parkinson's disease patients","volume":"320","author":"Takahashi","year":"2004","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1080\/10715760500260348","article-title":"Association of DJ-1 with chaperones and enhanced association and colocalization with mitochondrial Hsp70 by oxidative stress","volume":"39","author":"Li","year":"2005","journal-title":"Free Radic. Res."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"5215","DOI":"10.1073\/pnas.0501282102","article-title":"Hypersensitivity of DJ-1-deficient mice to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyrindine (MPTP) and oxidative stress","volume":"102","author":"Kim","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.nbd.2006.06.004","article-title":"PARK7 DJ-1 protects against degeneration of nigral dopaminergic neurons in Parkinson's disease rat model","volume":"24","author":"Inden","year":"2006","journal-title":"Neurobiol. Dis."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"14807","DOI":"10.1073\/pnas.0703219104","article-title":"DJ-1 gene deletion reveals that DJ-1 is an atypical peroxiredoxin-like peroxidase","volume":"104","author":"Andres","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"23:1","DOI":"10.1186\/1750-1326-4-23","article-title":"Dissembled DJ-1 high molecular weight complex in cortex mitochondria from Parkinson's disease patients","volume":"4","author":"Nural","year":"2009","journal-title":"Mol. Neurodegener."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"13670","DOI":"10.1073\/pnas.0504610102","article-title":"Inactivation of Drosophila DJ-1 leads to impairments of oxidative stress response and phosphatidylinositol 3-kinase\/Akt signaling","volume":"102","author":"Yang","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1038\/ng1778","article-title":"Mitochondrial DNA deletions are abundant and cause functional impairment in aged human substantia nigra neurons","volume":"38","author":"Kraytsberg","year":"2006","journal-title":"Nat. Genet."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1038\/ng1769","article-title":"High levels of mitochondrial DNA deletions in substantia nigra neurons in aging and Parkinson disease","volume":"38","author":"Bender","year":"2006","journal-title":"Nat. Genet."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"1787","DOI":"10.1212\/WNL.53.8.1787","article-title":"Familial multisystem degeneration with parkinsonism associated with the 11778 mitochondrial DNA mutation","volume":"53","author":"Simon","year":"1999","journal-title":"Neurology"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"1152","DOI":"10.1212\/01.wnl.0000276955.23735.eb","article-title":"Mitochondrial DNA polymerase gamma variants in idiopathic sporadic Parkinson disease","volume":"69","author":"Luoma","year":"2007","journal-title":"Neurology"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.1073\/pnas.0605208103","article-title":"Progressive parkinsonism in mice with respiratory-chain-deficient dopamine neurons","volume":"104","author":"Ekstrand","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1016\/j.expneurol.2006.08.015","article-title":"Mitochondria mass is low in mouse substantia nigra dopamine neurons: Implications for Parkinson's disease","volume":"203","author":"Liang","year":"2007","journal-title":"Exp. Neurol."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"30773","DOI":"10.1074\/jbc.M504749200","article-title":"Mitochondrial respiration and ATP production are significantly impaired in striatal cells expressing mutant huntingtin","volume":"280","author":"Milakovic","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.cell.2006.09.015","article-title":"Transcriptional repression of PGC-1alpha by mutant huntingtin leads to mitochondrial dysfunction and neurodegeneration","volume":"127","author":"Cui","year":"2006","journal-title":"Cell"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"11653","DOI":"10.1523\/JNEUROSCI.23-37-11653.2003","article-title":"Neuronal induction of the immunoproteasome in Huntington's disease","volume":"23","author":"Ferrer","year":"2003","journal-title":"J. Neurosci."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1093\/hmg\/ddi064","article-title":"Neuronal dysfunction in a polyglutamine disease model occurs in the absence of ubiquitin-proteasome system impairment and inversely correlates with the degree of nuclear inclusion formation","volume":"14","author":"Bowman","year":"2005","journal-title":"Hum. Mol. Genet."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"13986","DOI":"10.1073\/pnas.0906463106","article-title":"Accumulation of ubiquitin conjugates in a polyglutamine disease model occurs without global ubiquitin\/proteasome system impairment","volume":"106","author":"Maynard","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"2689","DOI":"10.1212\/WNL.43.12.2689","article-title":"Evidence for impairment of energy metabolism in vivo in Huntington's disease using localized 1H NMR spectroscopy","volume":"43","author":"Jenkins","year":"1993","journal-title":"Neurology"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1002\/ana.410120504","article-title":"Cerebral metabolism and atrophy in Huntington's disease determined by 18FDG and computed tomographic scan","volume":"12","author":"Kuhl","year":"1982","journal-title":"Ann. Neurol."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1002\/ana.410150723","article-title":"Patterns of cerebral glucose utilization in Parkinson's disease and Huntington's disease","volume":"15","author":"Kuhl","year":"1984","journal-title":"Ann. Neurol."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"1231","DOI":"10.1212\/WNL.40.8.1231","article-title":"Evidence for a defect in NADH: Ubiquinone oxidoreductase (complex I) in Huntington's disease","volume":"40","author":"Parker","year":"1990","journal-title":"Neurology"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1002\/ana.410390317","article-title":"Mitochondrial defect in Huntington's disease caudate nucleus","volume":"39","author":"Gu","year":"1996","journal-title":"Ann. Neurol."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1002\/ana.410410514","article-title":"Oxidative damage and metabolic dysfunction in Huntington's disease: Selective vulnerability of the basal ganglia","volume":"41","author":"Browne","year":"1997","journal-title":"Ann. Neurol."},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"1652","DOI":"10.1091\/mbc.e05-07-0607","article-title":"Involvement of mitochondrial complex II defects in neuronal death produced by N-terminus fragment of mutated huntingtin","volume":"17","author":"Benchoua","year":"2006","journal-title":"Mol. Biol. Cell"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1006\/exnr.2000.7626","article-title":"Early degenerative changes in transgenic mice expressing mutant huntingtin involve dendritic abnormalities but no impairment of mitochondrial energy production","volume":"169","author":"Guidetti","year":"2001","journal-title":"Exp. Neurol."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1038\/nn884","article-title":"Early mitochondrial calcium defects in Huntington's disease are a direct effect of polyglutamines","volume":"5","author":"Panov","year":"2002","journal-title":"Nat. Neurosci."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"4028","DOI":"10.1016\/S0021-9258(18)89226-2","article-title":"Regulation of oxidative phosphorylation in mitochondria by external free Ca2+ concentrations","volume":"260","author":"Moreno","year":"1985","journal-title":"J. Biol. Chem."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"1927","DOI":"10.1093\/hmg\/11.17.1927","article-title":"Polyglutamine and transcription: Gene expression changes shared by DRPLA and Huntington's disease mouse models reveal context-independent effects","volume":"11","author":"Luthi","year":"2002","journal-title":"Hum. Mol. Genet."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/S0168-9525(03)00074-X","article-title":"Transcriptional abnormalities in Huntington disease","volume":"19","author":"Sugars","year":"2003","journal-title":"Trends Genet."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.neuron.2005.06.005","article-title":"p53 mediates cellular dysfunction and behavioral abnormalities in Huntington's disease","volume":"47","author":"Bae","year":"2005","journal-title":"Neuron"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2008\/418765","article-title":"Peroxisome Proliferator-Activated Receptor-gamma in Amyotrophic Lateral Sclerosis and Huntington's Disease","volume":"2008","author":"Kiaei","year":"2008","journal-title":"PPAR Res."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1212\/WNL.47.2.535","article-title":"Impairment of fast axonal transport in the proximal axons of anterior horn neurons in amyotrophic lateral sclerosis","volume":"47","author":"Sasaki","year":"1996","journal-title":"Neurology"},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1471-2202-4-16","article-title":"ALS-associated mutant SOD1G93A causes mitochondrial vacuolation by expansion of the intermembrane space and by involvement of SOD1 aggregation and peroxisomes","volume":"4","author":"Higgins","year":"2003","journal-title":"BMC Neurosci."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1007\/s004010100399","article-title":"CuZn superoxide dismutase (SOD1) accumulates in vacuolated mitochondria in transgenic mice expressing amyotrophic lateral sclerosis-linked SOD1 mutations","volume":"102","author":"Jaarsma","year":"2001","journal-title":"Acta Neuropathol."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1016\/j.neuron.2004.06.016","article-title":"Toxicity of familial ALS-linked SOD1 mutants from selective recruitment to spinal mitochondria","volume":"43","author":"Liu","year":"2004","journal-title":"Neuron"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1007\/s00401-004-0837-z","article-title":"Ultrastructural study of mitochondria in the spinal cord of transgenic mice with a G93A mutant SOD1 gene","volume":"107","author":"Sasaki","year":"2004","journal-title":"Acta Neuropathol."},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"29626","DOI":"10.1074\/jbc.M203065200","article-title":"Mutated human SOD1 causes dysfunction of oxidative phosphorylation in mitochondria of transgenic mice","volume":"277","author":"Mattiazzi","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"1349","DOI":"10.1111\/j.1471-4159.2006.03619.x","article-title":"Neural mitochondrial Ca2+ capacity impairment precedes the onset of motor symptoms in G93A Cu\/Zn-superoxide dismutase mutant mice","volume":"96","author":"Damiano","year":"2006","journal-title":"J. Neurochem."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"2007","DOI":"10.1073\/pnas.0810934106","article-title":"The Psi(m) depolarization that accompanies mitochondrial Ca2+ uptake is greater in mutant SOD1 than in wild-type mouse motor terminals","volume":"106","author":"Nguyen","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"2720","DOI":"10.1093\/hmg\/ddm226","article-title":"Familial amyotrophic lateral sclerosis-linked SOD1 mutants perturb fast axonal transport to reduce axonal mitochondria content","volume":"16","author":"Chapman","year":"2007","journal-title":"Hum. Mol. Genet."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"4022","DOI":"10.1073\/pnas.0712209105","article-title":"Selective association of misfolded ALS-linked mutant SOD1 with the cytoplasmic face of mitochondria","volume":"105","author":"Vande","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.neuron.2004.06.021","article-title":"Amyotrophic lateral sclerosis-associated SOD1 mutant proteins bind and aggregate with Bcl-2 in spinal cord mitochondria","volume":"43","author":"Pasinelli","year":"2004","journal-title":"Neuron"},{"key":"ref_160","doi-asserted-by":"crossref","first-page":"50966","DOI":"10.1074\/jbc.M209356200","article-title":"Mitochondrial localization of mutant superoxide dismutase 1 triggers caspase-dependent cell death in a cellular model of familial amyotrophic lateral sclerosis","volume":"277","author":"Takeuchi","year":"2002","journal-title":"J Biol Chem"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"5737","DOI":"10.1073\/pnas.75.11.5737","article-title":"Identification of insulin in rat brain","volume":"75","author":"Havrankova","year":"1978","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"8445","DOI":"10.1016\/S0021-9258(17)37214-9","article-title":"Insulin gene expression and insulin synthesis in mammalian neuronal cells","volume":"269","author":"Devaskar","year":"1994","journal-title":"J. Biol. Chem."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1210\/endo-123-1-505","article-title":"Insulin synthesis by isolated rabbit neurons","volume":"123","author":"Schechter","year":"1988","journal-title":"Endocrinology"},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1038\/272827a0","article-title":"Insulin receptors are widely distributed in th central nervous system of the rat","volume":"272","author":"Havrankova","year":"1978","journal-title":"Nature"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"636","DOI":"10.1172\/JCI109504","article-title":"Concentrations of insulin and insulin receptors in the brain are independent of peripheral insulin levels. Studies of obese and streptozotocin-treated rodents","volume":"64","author":"Havrankova","year":"1979","journal-title":"J. Clin. Invest."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.tem.2005.01.008","article-title":"The role of insulin receptor signaling in the brain","volume":"16","author":"Plum","year":"2005","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/S0303-7207(01)00455-5","article-title":"Role of insulin and insulin receptor in learning and memory","volume":"177","author":"Zhao","year":"2001","journal-title":"Mol. Cell Endocrinol."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1016\/j.neubiorev.2007.04.004","article-title":"Molecular connexions between dementia and diabetes","volume":"31","author":"Cole","year":"2007","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/S0736-5748(02)00047-3","article-title":"Functions of PI 3-kinase in development of the nervous system","volume":"20","author":"Rodgers","year":"2002","journal-title":"Int. J. Dev. Neurosci."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.ejphar.2008.01.050","article-title":"Brain insulin, energy and glucose homeostasis; genes, environment and metabolic pathologies","volume":"585","author":"Gerozissis","year":"2008","journal-title":"Eur. J. Pharmacol."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1007\/s12640-009-9060-y","article-title":"IGF-1 and pAKT Signaling Promote Hippocampal CA1 Neuronal Survival Following Injury to Dentate Granule Cells","volume":"16","author":"Wine","year":"2009","journal-title":"Neurotox. Res."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.ejphar.2004.02.042","article-title":"Signaling by insulin-like growth factor 1 in brain","volume":"490","author":"Bondy","year":"2004","journal-title":"Eur. J. Pharmacol."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1016\/S0165-6147(02)02037-0","article-title":"Does insulin dysfunction play a role in Alzheimer's disease?","volume":"23","author":"Gasparini","year":"2002","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"19547","DOI":"10.1074\/jbc.272.31.19547","article-title":"Insulin and insulin-like growth factor-1 regulate tau phosphorylation in cultured human neurons","volume":"272","author":"Hong","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1126\/science.1078223","article-title":"Extended longevity in mice lacking the insulin receptor in adipose tissue","volume":"299","author":"Kahn","year":"2003","journal-title":"Science"},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1038\/nature01298","article-title":"IGF-1 receptor regulates lifespan and resistance to oxidative stress in mice","volume":"421","author":"Holzenberger","year":"2003","journal-title":"Nature"},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"10417","DOI":"10.1073\/pnas.152161099","article-title":"The threshold for polyglutamine-expansion protein aggregation and cellular toxicity is dynamic and influenced by aging in Caenorhabditis elegans","volume":"99","author":"Morley","year":"2002","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"1604","DOI":"10.1126\/science.1124646","article-title":"Opposing activities protect against age onset proteotoxicity","volume":"313","author":"Cohen","year":"2006","journal-title":"Science"},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"3315","DOI":"10.1096\/fj.09-132043","article-title":"Neuronal IGF-1 resistance reduces Abeta accumulation and protects against premature death in a model of Alzheimer's disease","volume":"23","author":"Freude","year":"2009","journal-title":"FASEB J."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1101\/lm.6.5.478","article-title":"A necessity for MAP kinase activation in mammalian spatial learning","volume":"6","author":"Selcher","year":"1999","journal-title":"Learn. Mem."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1038\/2836","article-title":"The MAPK cascade is required for mammalian associative learning","volume":"1","author":"Atkins","year":"1998","journal-title":"Nat. Neurosci."},{"key":"ref_182","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1744-8069-3-36","article-title":"Requirement of extracellular signal-regulated kinase\/mitogen-activated protein kinase for long-term potentiation in adult mouse anterior cingulate cortex","volume":"3","author":"Toyoda","year":"2007","journal-title":"Mol. Pain"},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"1617","DOI":"10.1111\/j.1460-9568.2006.05055.x","article-title":"ERK1\/2 but not p38 MAP kinase is essential for the long-term depression in mouse cerebellar slices","volume":"24","author":"Ito","year":"2006","journal-title":"Eur. J. Neurosci."},{"key":"ref_184","doi-asserted-by":"crossref","first-page":"34893","DOI":"10.1074\/jbc.274.49.34893","article-title":"Brain insulin receptors and spatial memory. Correlated changes in gene expression, tyrosine phosphorylation, and signaling molecules in the hippocampus of water maze trained rats","volume":"274","author":"Zhao","year":"1999","journal-title":"J. Biol. Chem."},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/S0031-9384(99)00220-6","article-title":"Intracerebroventricular insulin enhances memory in a passive-avoidance task","volume":"68","author":"Park","year":"2000","journal-title":"Physiol. Behav."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1016\/j.bandc.2007.01.002","article-title":"Intrahippocampal insulin improves memory in a passive-avoidance task in male wistar rats","volume":"64","author":"Babri","year":"2007","journal-title":"Brain Cogn."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1001\/archpsyc.56.12.1135","article-title":"Enhancement of memory in Alzheimer disease with insulin and somatostatin, but not glucose","volume":"56","author":"Craft","year":"1999","journal-title":"Arch. Gen. Psychiatry"},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/S0014-2999(00)00540-9","article-title":"Manipulating neuropeptidergic pathways in humans: A novel approach to neuropharmacology?","volume":"405","author":"Fehm","year":"2000","journal-title":"Eur. J. Pharmacol."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"1326","DOI":"10.1016\/j.psyneuen.2004.04.003","article-title":"Intranasal insulin improves memory in humans","volume":"29","author":"Benedict","year":"2004","journal-title":"Psychoneuroendocrinology"},{"key":"ref_190","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1159\/000106378","article-title":"Intranasal insulin to improve memory function in humans","volume":"86","author":"Benedict","year":"2007","journal-title":"Neuroendocrinology"},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.ejphar.2008.01.051","article-title":"Insulin, PKC signaling pathways and synaptic remodeling during memory storage and neuronal repair","volume":"585","author":"Nelson","year":"2008","journal-title":"Eur. J. Pharmacol."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/S1474-4422(04)00681-7","article-title":"Insulin and neurodegenerative disease: Shared and specific mechanisms","volume":"3","author":"Craft","year":"2004","journal-title":"Lancet Neurol."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1007\/BF00972477","article-title":"Insulin receptors in the brain: Structural and physiological characterization","volume":"13","author":"Raizada","year":"1988","journal-title":"Neurochem. Res."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/0006-8993(89)90308-9","article-title":"Reduction of insulin binding in the arcuate nucleus of the rat hypothalamus after 6-hydroxydopamine treatment","volume":"500","author":"Wilcox","year":"1989","journal-title":"Brain Res."},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1055\/s-2007-978749","article-title":"Neurotransmitter transporters: Target for endocrine regulation","volume":"31","author":"Figlewicz","year":"1999","journal-title":"Horm. Metab. Res."},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/j.npep.2009.05.006","article-title":"In vivo electrophysiological effects of insulin in the rat brain","volume":"43","author":"Kovacs","year":"2009","journal-title":"Neuropeptides"},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1016\/j.neuroscience.2008.07.022","article-title":"Increased glutamate receptor gene expression in the cerebral cortex of insulin induced hypoglycemic and streptozotocin-induced diabetic rats","volume":"156","author":"Joseph","year":"2008","journal-title":"Neuroscience"},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1074\/jbc.M807914200","article-title":"Glutamate acting on N-methyl-D-aspartate receptors attenuates insulin-like growth factor-1 receptor tyrosine phosphorylation and its survival signaling properties in rat hippocampal neurons","volume":"284","author":"Zheng","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"475","DOI":"10.5483\/BMBRep.2009.42.8.475","article-title":"Insulin resistance and Alzheimer's disease","volume":"42","year":"2009","journal-title":"BMB Rep."},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1007\/s00109-004-0552-1","article-title":"Neurodegenerative disorders associated with diabetes mellitus","volume":"82","author":"Ristow","year":"2004","journal-title":"J. Mol. Med."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.exger.2006.08.009","article-title":"The role of insulin and neurotrophic factor signaling in brain aging and Alzheimer's Disease","volume":"42","author":"Cole","year":"2007","journal-title":"Exp. Gerontol."},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/S0002-9440(10)63822-9","article-title":"Reduced hippocampal insulin-degrading enzyme in late-onset Alzheimer's disease is associated with the apolipoprotein E-epsilon4 allele","volume":"162","author":"Cook","year":"2003","journal-title":"Am. J. Pathol."},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1016\/S0896-6273(03)00787-6","article-title":"Enhanced proteolysis of beta amyloid in APP transgenic mice prevents plaque formation, secondary pathology, and premature death","volume":"40","author":"Leissring","year":"2003","journal-title":"Neuron"},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"6641","DOI":"10.1074\/jbc.272.10.6641","article-title":"Degradation of amyloid beta-protein by a metalloprotease secreted by microglia and other neural and non-neural cells","volume":"272","author":"Qiu","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1096\/fj.03-0978fje","article-title":"Diet-induced insulin resistance promotes amyloidosis in a transgenic mouse model of Alzheimer's disease","volume":"18","author":"Ho","year":"2004","journal-title":"FASEB J."},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1046\/j.1471-4159.2001.00472.x","article-title":"Effect of the Alzheimer amyloid fragment Abeta(25-35) on Akt\/PKB kinase and survival of PC12 cells","volume":"78","author":"Salinas","year":"2001","journal-title":"J. Neurochem."},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"1533","DOI":"10.1091\/mbc.e08-07-0777","article-title":"The insulin\/Akt signaling pathway is targeted by intracellular beta-amyloid","volume":"20","author":"Lee","year":"2009","journal-title":"Mol. Biol. Cell"},{"key":"ref_208","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1007\/s004010100435","article-title":"The active form of glycogen synthase kinase-3beta is associated with granulovacuolar degeneration in neurons in Alzheimer's disease","volume":"103","author":"Leroy","year":"2002","journal-title":"Acta Neuropathol."},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1093\/emboj\/20.1.27","article-title":"Decreased nuclear beta-catenin, tau hyperphosphorylation and neurodegeneration in GSK-3beta conditional transgenic mice","volume":"20","author":"Lucas","year":"2001","journal-title":"EMBO J."},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1111\/j.1471-4159.2005.03637.x","article-title":"Alzheimer-like changes in protein kinase B and glycogen synthase kinase-3 in rat frontal cortex and hippocampus after damage to the insulin signalling pathway","volume":"96","author":"Salkovic","year":"2006","journal-title":"J. Neurochem."},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"757","DOI":"10.1111\/j.1471-4159.2006.04368.x","article-title":"Brain insulin system dysfunction in streptozotocin intracerebroventricularly treated rats generates hyperphosphorylated tau protein","volume":"101","author":"Salkovic","year":"2007","journal-title":"J. Neurochem."},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"19547","DOI":"10.1074\/jbc.272.31.19547","article-title":"Insulin and insulin-like growth factor-1 regulate tau phosphorylation in cultured human neurons","volume":"272","author":"Hong","year":"1997","journal-title":"J. Biol. Chem."},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"1256","DOI":"10.2337\/diabetes.51.4.1256","article-title":"Honolulu-Asia Aging Study. Type 2 diabetes, APOE gene, and the risk for dementia and related pathologies: The Honolulu-Asia Aging Study","volume":"51","author":"Peila","year":"2002","journal-title":"Diabetes"},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1038\/nrm2101","article-title":"Soluble protein oligomers in neurodegeneration: Lessons from the Alzheimer's amyloid beta-peptide","volume":"8","author":"Haass","year":"2007","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"1971","DOI":"10.1073\/pnas.0809158106","article-title":"Protection of synapses against Alzheimer\u2019s-linked toxins: Insulin signaling prevents the pathogenic binding of Abeta oligomers","volume":"106","author":"Vieira","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_216","doi-asserted-by":"crossref","first-page":"63","DOI":"10.3233\/JAD-2005-7107","article-title":"Impaired insulin and insulin-like growth factor expression and signaling mechanisms in Alzheimer's disease\u2014Is this type 3 diabetes?","volume":"7","author":"Steen","year":"2005","journal-title":"J. Alzheimers Dis."},{"key":"ref_217","doi-asserted-by":"crossref","first-page":"125","DOI":"10.3109\/00207459309003322","article-title":"The relationship between diabetes mellitus and Parkinson's disease","volume":"69","author":"Sandyk","year":"1993","journal-title":"Int. J. Neurosci."},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1097\/00005053-196006000-00017","article-title":"Progression and prognosis in Parkinson's disease","volume":"130","author":"Schwab","year":"1960","journal-title":"J. Nerv. Ment. Dis."},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1007\/BF00313602","article-title":"Loss of insulin receptor immunoreactivity from the substantia nigra pars compacta neurons in Parkinson's disease","volume":"87","author":"Moroo","year":"1994","journal-title":"Acta Neuropathol."},{"key":"ref_220","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1159\/000054415","article-title":"Intracerebroventricular administration of bromocriptine ameliorates the insulin-resistant\/glucose-intolerant state in hamsters","volume":"69","author":"Luo","year":"1999","journal-title":"Neuroendocrinology"},{"key":"ref_221","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/0006-8993(94)91698-5","article-title":"Intraventricular insulin increases dopamine transporter mRNA in rat VTA\/substantia nigra","volume":"644","author":"Figlewicz","year":"1994","journal-title":"Brain Res."},{"key":"ref_222","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/0006-8993(96)00727-5","article-title":"Diabetes causes differential changes in CNS noradrenergic and dopaminergic neurons in the rat: A molecular study","volume":"736","author":"Figlewicz","year":"1996","journal-title":"Brain Res."},{"key":"ref_223","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/0304-3940(95)12232-X","article-title":"Diabetes decreases limbic extracellular dopamine in rats","volume":"202","author":"Murzi","year":"1996","journal-title":"Neurosci. Lett."},{"key":"ref_224","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/S0149-7634(01)00016-1","article-title":"Cognitive effects of insulin in the central nervous system","volume":"25","author":"Park","year":"2001","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_225","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1111\/j.1399-0004.1985.tb00185.x","article-title":"Diabetes mellitus in Huntington disease","volume":"27","author":"Farrer","year":"1985","journal-title":"Clin. Genet."},{"key":"ref_226","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1159\/000212174","article-title":"Abnormal glucose tolerance and arginine tolerance tests in Huntington's disease","volume":"23","author":"Podolsky","year":"1977","journal-title":"Gerontology"},{"key":"ref_227","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1001\/archneur.65.4.476","article-title":"Glucose homeostasis in Huntington disease: Abnormalities in insulin sensitivity and early-phase insulin secretion","volume":"65","author":"Svetel","year":"2008","journal-title":"Arch. Neurol."},{"key":"ref_228","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1016\/S1534-5807(02)00188-0","article-title":"The IGF-1\/Akt pathway is neuroprotective in Huntington's disease and involves Huntingtin phosphorylation by Akt","volume":"2","author":"Humbert","year":"2002","journal-title":"Dev. Cell."},{"key":"ref_229","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1083\/jcb.200510065","article-title":"Autophagy-mediated clearance of huntingtin aggregates triggered by the insulin-signaling pathway","volume":"172","author":"Yamamoto","year":"2006","journal-title":"J. Cell Biol."},{"key":"ref_230","doi-asserted-by":"crossref","first-page":"1478","DOI":"10.1111\/j.1460-9568.2005.03985.x","article-title":"Akt is altered in an animal model of Huntington's disease and in patients","volume":"21","author":"Colin","year":"2005","journal-title":"Eur. J. Neurosci."},{"key":"ref_231","doi-asserted-by":"crossref","unstructured":"Pradat, P.F., Bruneteau, G., Gordon, P.H., Dupuis, L., Bonnefont, R.D., Simon, D., Salachas, F., Corcia, P., Frochot, V., Lacorte, J.M., Jardel, C., Coussieu, C., Forestier, N.L., Lacomblez, L., Loeffler, J.P., and Meininger, V. (2009). Impaired glucose tolerance in patients with amyotrophic lateral sclerosis. Amyotroph. Lateral. Scler., 1\u20136.","DOI":"10.1080\/17482960902822960"},{"key":"ref_232","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1016\/j.nbd.2004.03.001","article-title":"IGF-I prevents glutamate-induced motor neuron programmed cell death","volume":"16","author":"Vincent","year":"2004","journal-title":"Neurobiol. Dis."},{"key":"ref_233","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1126\/science.1086137","article-title":"Retrograde viral delivery of IGF-1 prolongs survival in a mouse ALS model","volume":"301","author":"Kaspar","year":"2003","journal-title":"Science."},{"key":"ref_234","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.mce.2008.11.025","article-title":"Insulin\/IGF-1 and ROS signaling pathway cross-talk in aging and longevity determination","volume":"299","author":"Papaconstantinou","year":"2009","journal-title":"Mol. Cell Endocrinol."},{"key":"ref_235","doi-asserted-by":"crossref","first-page":"45","DOI":"10.3233\/JAD-2005-7106","article-title":"Review of insulin and insulin-like growth factor expression, signaling, and malfunction in the central nervous system: Relevance to Alzheimer's disease","volume":"7","author":"Wands","year":"2005","journal-title":"J. Alzheimers Dis."},{"key":"ref_236","doi-asserted-by":"crossref","first-page":"2620","DOI":"10.1210\/en.2007-1563","article-title":"Low doses of insulin-like growth factor-I induce mitochondrial protection in aging rats","volume":"149","author":"Puche","year":"2008","journal-title":"Endocrinology"},{"key":"ref_237","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1016\/j.nbd.2004.10.017","article-title":"Insulin protects against amyloid beta-peptide toxicity in brain mitochondria of diabetic rats","volume":"18","author":"Moreira","year":"2005","journal-title":"Neurobiol. Dis."},{"key":"ref_238","doi-asserted-by":"crossref","first-page":"299","DOI":"10.2174\/157340606776930754","article-title":"Insulin attenuates diabetes-related mitochondrial alterations: A comparative study","volume":"2","author":"Moreira","year":"2006","journal-title":"Med. Chem."},{"key":"ref_239","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1111\/j.1471-4159.2008.05473.x","article-title":"Insulin blocks cytochrome c release in the reperfused brain through PI3-K signaling and by promoting Bax\/Bcl-XL binding","volume":"106","author":"Sanderson","year":"2008","journal-title":"J. Neurochem."},{"key":"ref_240","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.1046\/j.1471-4159.2003.02113.x","article-title":"Rapid accumulation of Akt in mitochondria following phosphatidylinositol 3-kinase activation","volume":"87","author":"Bijur","year":"2003","journal-title":"J. Neurochem."},{"key":"ref_241","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1089\/152091503763816481","article-title":"Therapeutic potential of peroxisome proliferator-activated receptor agonists for neurological disease","volume":"5","author":"Feinstein","year":"2003","journal-title":"Diabetes Technol. Ther."},{"key":"ref_242","doi-asserted-by":"crossref","first-page":"1343","DOI":"10.2174\/138955708786369546","article-title":"Mechanisms of action of metformin in type 2 diabetes and associated complications: An overview","volume":"8","author":"Correia","year":"2008","journal-title":"Mini Rev. Med. Chem."},{"key":"ref_243","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1016\/0092-8674(95)90193-0","article-title":"15-Deoxy-delta 12, 14-prostaglandin J2 is a ligand for the adipocyte determination factor PPAR gamma","volume":"83","author":"Forman","year":"1995","journal-title":"Cell"},{"key":"ref_244","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1016\/0092-8674(95)90194-9","article-title":"A prostaglandin J2 metabolite binds peroxisome proliferator-activated receptor gamma and promotes adipocyte differentiation","volume":"83","author":"Kliewer","year":"1995","journal-title":"Cell"},{"key":"ref_245","doi-asserted-by":"crossref","first-page":"42464","DOI":"10.1074\/jbc.M504212200","article-title":"Fatty acid transduction of nitric oxide signaling: Multiple nitrated unsaturated fatty acid derivatives exist in human blood and urine and serve as endogenous peroxisome proliferator-activated receptor ligands","volume":"280","author":"Baker","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_246","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1523\/JNEUROSCI.20-02-00558.2000","article-title":"Inflammatory mechanisms in Alzheimer's disease: Inhibition of beta-amyloid-stimulated proinflammatory responses and neurotoxicity by PPARgamma agonists","volume":"20","author":"Combs","year":"2000","journal-title":"J. Neurosci."},{"key":"ref_247","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.jneuroim.2004.12.015","article-title":"Peroxisome proliferator-activated receptor-gamma agonists inhibit the activation of microglia and astrocytes: Implications for multiple sclerosis","volume":"161","author":"Storer","year":"2005","journal-title":"J. Neuroimmunol."},{"key":"ref_248","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1002\/jnr.20518","article-title":"Agonists for the peroxisome proliferator-activated receptor-alpha and the retinoid X receptor inhibit inflammatory responses of microglia","volume":"81","author":"Xu","year":"2005","journal-title":"J. Neurosci. Res."},{"key":"ref_249","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/S0165-5728(99)00192-7","article-title":"Peroxisome proliferator-activated receptor gamma agonists protect cerebellar granule cells from cytokine-induced apoptotic cell death by inhibition of inducible nitric oxide synthase","volume":"100","author":"Heneka","year":"1999","journal-title":"J. Neuroimmunol."},{"key":"ref_250","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1016\/j.brainres.2005.12.061","article-title":"Peroxisome-proliferator-activated receptor-gamma (PPAR\u03b3) activation protects neurons from NMDA excitotoxicity","volume":"1073\/1074","author":"Zhao","year":"2006","journal-title":"Brain Research"},{"key":"ref_251","doi-asserted-by":"crossref","first-page":"31781","DOI":"10.1074\/jbc.M204279200","article-title":"Thiazolidinedione Activation of Peroxisome Proliferator-activated Receptor \u03b3 Can Enhance Mitochondrial Potential and Promote Cell Survival","volume":"277","author":"Wang","year":"2002","journal-title":"J. Biol.Chem."},{"key":"ref_252","doi-asserted-by":"crossref","first-page":"37006","DOI":"10.1074\/jbc.M700447200","article-title":"Peroxisome Proliferator-activated Receptor \u03b3 Up-regulates the Bcl-2 Anti-apoptotic Protein in Neurons and Induces Mitochondrial Stabilization and Protection against Oxidative Stress and Apoptosis","volume":"282","author":"Fuenzalida","year":"2007","journal-title":"J. Biol.Chem."},{"key":"ref_253","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1002\/jcp.21730","article-title":"Rosiglitazone and PPAR-gamma overexpression protect mitochondrial membrane potential and prevent apoptosis by upregulating anti-apoptotic Bcl-2 family proteins","volume":"220","author":"Wu","year":"2009","journal-title":"J. Cell Physiol."},{"key":"ref_254","doi-asserted-by":"crossref","first-page":"1695","DOI":"10.1124\/mol.106.033845","article-title":"The Thiazolidinedione Pioglitazone Alters Mitochondrial Function in Human Neuron-Like Cells","volume":"71","author":"Ghosh","year":"2007","journal-title":"Mol. Pharmacol."},{"key":"ref_255","doi-asserted-by":"crossref","first-page":"1442","DOI":"10.1093\/brain\/awh452","article-title":"Acute treatment with the PPARgamma agonist pioglitazone and ibuprofen reduces glial inflammation and Abeta1-42 levels in APPV717I transgenic mice","volume":"128","author":"Heneka","year":"2005","journal-title":"Brain"},{"key":"ref_256","doi-asserted-by":"crossref","first-page":"93","DOI":"10.2174\/138161206780574579","article-title":"PPAR-gamma agonists as regulators of microglial activation and brain inflammation","volume":"12","author":"Bernardo","year":"2006","journal-title":"Curr. Pharm. Des."},{"key":"ref_257","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1016\/j.bbalip.2007.04.016","article-title":"PPARs in the brain","volume":"1771","author":"Heneka","year":"2007","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_258","doi-asserted-by":"crossref","first-page":"7504","DOI":"10.1523\/JNEUROSCI.23-20-07504.2003","article-title":"Anti-inflammatory drug therapy alters beta-amyloid processing and deposition in an animal model of Alzheimer's disease","volume":"23","author":"Yan","year":"2003","journal-title":"J. Neurosci."},{"key":"ref_259","doi-asserted-by":"crossref","first-page":"9796","DOI":"10.1523\/JNEUROSCI.23-30-09796.2003","article-title":"Nonsteroidal anti-inflammatory drugs and peroxisome proliferator-activated receptor-gamma agonists modulate immunostimulated processing of amyloid precursor protein through regulation of beta-secretase","volume":"23","author":"Sastre","year":"2003","journal-title":"J. Neurosci."},{"key":"ref_260","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.yexcr.2004.09.032","article-title":"Peroxisome proliferator-activated receptor gamma is expressed in hippocampal neurons and its activation prevents beta-amyloid neurodegeneration: Role of Wnt signaling","volume":"304","author":"Inestrosa","year":"2005","journal-title":"Exp. Cell Res."},{"key":"ref_261","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1523\/JNEUROSCI.20-02-00558.2000","article-title":"Inflammatory mechanisms in Alzheimer's disease: Inhibition of beta-amyloid-stimulated proinflammatory responses and neurotoxicity by PPARgamma agonists","volume":"20","author":"Combs","year":"2000","journal-title":"J. Neurosci."},{"key":"ref_262","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2008\/403896","article-title":"PPARs in Alzheimer\u2019s Disease","volume":"2008","author":"Kummer","year":"2008","journal-title":"PPAR Res."},{"key":"ref_263","doi-asserted-by":"crossref","first-page":"45","DOI":"10.3233\/JAD-2007-11108","article-title":"Rosiglitazone induces mitochondrial biogenesis in mouse brain","volume":"11","author":"Strum","year":"2007","journal-title":"J. Alzheimers Dis."},{"key":"ref_264","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1210\/er.2006-0037","article-title":"Peroxisome proliferator-activated receptor gamma coactivator 1 coactivators, energy homeostasis, and metabolism","volume":"27","author":"Handschin","year":"2006","journal-title":"Endocr. Rev."},{"key":"ref_265","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1001\/archneurol.2008.588","article-title":"PGC-1alpha expression decreases in the Alzheimer disease brain as a function of dementia","volume":"66","author":"Qin","year":"2009","journal-title":"Arch. Neurol."},{"key":"ref_266","first-page":"950","article-title":"Preserved cognition in patients with early Alzheimer disease and amnestic mild cognitive impairment during treatment with rosiglitazone: A preliminary study","volume":"13","author":"Watson","year":"2005","journal-title":"Am. J. Geriatr. Psychiatry"},{"key":"ref_267","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1038\/sj.tpj.6500369","article-title":"Efficacy of rosiglitazone in a genetically defined population with mild-to-moderate Alzheimer's disease","volume":"6","author":"Risner","year":"2006","journal-title":"Pharmacogenomics J."},{"key":"ref_268","first-page":"68","article-title":"Diabetes mellitus in parkinsonism patients","volume":"26","author":"Chalmanov","year":"1987","journal-title":"Vutr. Boles."},{"key":"ref_269","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/0304-3940(96)12357-0","article-title":"Insulin receptor mRNA in the substantia nigra in Parkinson's disease","volume":"204","author":"Takahashi","year":"1996","journal-title":"Neurosci. Lett."},{"key":"ref_270","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1111\/j.1749-6632.1999.tb07824.x","article-title":"Cellular and molecular mechanisms underlying perturbed energy metabolism and neuronal degeneration in Alzheimer's and Parkinson's diseases","volume":"893","author":"Mattson","year":"1999","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_271","doi-asserted-by":"crossref","first-page":"35","DOI":"10.2174\/157015907780077123","article-title":"Agonism of Peroxisome Proliferator Receptor\u2013Gamma may have Therapeutic Potential for Neuroinflammation and Parkinson\u2019s Disease","volume":"5","author":"Hunter","year":"2007","journal-title":"Current Neuropharmacology"},{"key":"ref_272","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1046\/j.1471-4159.2002.00990.x","article-title":"Protective action of the peroxisome proliferator-activated receptor-gamma agonist pioglitazone in a mouse model of Parkinson's disease","volume":"82","author":"Breidert","year":"2002","journal-title":"J. Neurochem."},{"key":"ref_273","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1046\/j.1471-4159.2003.02210.x","article-title":"Protection by pioglitazone in the MPTP model of Parkinson's disease correlates with I kappa B alpha induction and block of NF kappa B and iNOS activation","volume":"88","author":"Dehmer","year":"2004","journal-title":"J. Neurochem."},{"key":"ref_274","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1038\/bjp.2008.78","article-title":"The PPARgamma agonist pioglitazone is effective in the MPTP mouse model of Parkinson's disease through inhibition of monoamine oxidase B","volume":"154","author":"Quinn","year":"2008","journal-title":"Br. J. Pharmacol."},{"key":"ref_275","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.1111\/j.1471-4159.2006.04327.x","article-title":"Inflammation induces mitochondrial dysfunction and dopaminergic neurodegeneration in the nigrostriatal system","volume":"100","author":"Hunter","year":"2007","journal-title":"J. Neurochem."},{"key":"ref_276","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1016\/j.neulet.2007.12.019","article-title":"Protective properties afforded by pioglitazone against intrastriatal LPS in Sprague-Dawley rats","volume":"432","author":"Hunter","year":"2008","journal-title":"Neurosci. Lett."},{"key":"ref_277","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.jneuroim.2007.09.029","article-title":"Neuroprotection with pioglitazone against LPS insult on dopaminergic neurons may be associated with its inhibition of NF-kappaB and JNK activation and suppression of COX-2 activity","volume":"192","author":"Xing","year":"2007","journal-title":"J. Neuroimmunol."},{"key":"ref_278","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1742-2094-5-4","article-title":"Pioglitazone inhibition of lipopolysaccharide-induced nitric oxide synthase is associated with altered activity of p38 MAP kinase and PI3K\/Akt","volume":"5","author":"Xing","year":"2008","journal-title":"J. Neuroinflammation"},{"key":"ref_279","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1016\/j.bbrc.2005.11.177","article-title":"Rosiglitazone protects human neuroblastoma SH-SY5Y cells against acetaldehyde-induced cytotoxicity","volume":"340","author":"Jung","year":"2006","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_280","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/j.jns.2006.11.020","article-title":"Rosiglitazone protects human neuroblastoma SH-SY5Y cells against MPP+ induced cytotoxicity via inhibition of mitochondrial dysfunction and ROS production","volume":"253","author":"Jung","year":"2007","journal-title":"J. Neurol. Sci."},{"key":"ref_281","doi-asserted-by":"crossref","first-page":"1356","DOI":"10.1016\/S0140-6736(72)91092-6","article-title":"Increased frequency of diabetes mellitus in patients with Huntington's chorea","volume":"1","author":"Podolsky","year":"1972","journal-title":"Lancet"},{"key":"ref_282","doi-asserted-by":"crossref","first-page":"649","DOI":"10.2337\/diabetes.48.3.649","article-title":"Mice transgenic for an expanded CAG repeat in the Huntington\u2019s disease gene develop diabetes","volume":"48","author":"Hurlbert","year":"1999","journal-title":"Diabetes"},{"key":"ref_283","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1006\/nbdi.2002.0562","article-title":"Huntington's disease of the endocrine pancreas: Insulin deficiency and diabetes mellitus due to impaired insulin gene expression","volume":"11","author":"Andreassen","year":"2002","journal-title":"Neurobiol. Dis."},{"key":"ref_284","doi-asserted-by":"crossref","first-page":"25628","DOI":"10.1074\/jbc.M804291200","article-title":"Rosiglitazone treatment prevents mitochondrial dysfunction in mutant huntingtin-expressing cells: Possible role of peroxisome proliferator-activated receptor-gamma (PPARgamma) in the pathogenesis of Huntington disease","volume":"283","author":"Quintanilla","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_285","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1016\/j.cell.2006.10.023","article-title":"PGC, lalpha, a new therapeutic target in Huntington's disease?","volume":"127","author":"McGill","year":"2006","journal-title":"Cell"},{"key":"ref_286","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/j.cell.2006.09.024","article-title":"Suppression of reactive oxygen species and neurodegeneration by the PGC-1 transcriptional coactivators","volume":"127","author":"Drori","year":"2006","journal-title":"Cell"},{"key":"ref_287","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/j.cmet.2006.10.004","article-title":"Thermoregulatory and metabolic defects in Huntington\u2019s disease transgenic mice implicate PGC-1alpha in Huntington\u2019s disease neurodegeneration","volume":"4","author":"Weydt","year":"2006","journal-title":"Cell Metab"},{"key":"ref_288","doi-asserted-by":"crossref","first-page":"3:1","DOI":"10.1186\/1750-1326-4-3","article-title":"The gene coding for PGC-1alpha modifies age at onset in Huntington's Disease","volume":"4","author":"Weydt","year":"2009","journal-title":"Mol. Neurodegener."},{"key":"ref_289","first-page":"1","article-title":"PGC-1alpha as modifier of onset age in Huntington disease","volume":"4","author":"Taherzadeh","year":"2009","journal-title":"Mol. Neurodegener."},{"key":"ref_290","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1038\/ng1534","article-title":"Resveratrol rescues mutant polyglutamine cytotoxicity in nematode and mammalian neurons","volume":"37","author":"Parker","year":"2005","journal-title":"Nat. Genet."},{"key":"ref_291","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1042\/BJ20070140","article-title":"Sirtuins in mammals: Insights into their biological function","volume":"404","author":"Michan","year":"2007","journal-title":"Biochem. J."},{"key":"ref_292","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1038\/ncpneuro0586","article-title":"Drug insight: Effects mediated by peroxisome proliferator-activated receptor-gamma in CNS disorders","volume":"3","author":"Heneka","year":"2007","journal-title":"Nat. Clin. Pract. Neurol."},{"key":"ref_293","doi-asserted-by":"crossref","first-page":"7805","DOI":"10.1523\/JNEUROSCI.2038-05.2005","article-title":"The oral antidiabetic pioglitazone protects from neurodegeneration and amyotrophic lateral sclerosis-like symptoms in superoxide dismutase-G93A transgenic mice","volume":"25","author":"Reimann","year":"2005","journal-title":"J. Neurosci."},{"key":"ref_294","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.expneurol.2004.10.007","article-title":"Peroxisome proliferator-activated receptor-gamma agonist extends survival in transgenic mouse model of amyotrophic lateral sclerosis","volume":"191","author":"Kiaei","year":"2005","journal-title":"Exp. Neurol."},{"key":"ref_295","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1038\/nrn1971","article-title":"Molecular biology of amyotrophic lateral sclerosis: Insights from genetics","volume":"7","author":"Pasinelli","year":"2006","journal-title":"Nat. Rev. Neurosci."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/2\/3\/250\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T22:12:05Z","timestamp":1760220725000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/2\/3\/250"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,12,23]]},"references-count":295,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2009,12]]}},"alternative-id":["ph2030250"],"URL":"https:\/\/doi.org\/10.3390\/ph2030250","relation":{},"ISSN":["1424-8247"],"issn-type":[{"type":"electronic","value":"1424-8247"}],"subject":[],"published":{"date-parts":[[2009,12,23]]}}}