{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T22:31:27Z","timestamp":1791930687437,"version":"4.3.4"},"reference-count":72,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2017,3,3]],"date-time":"2017-03-03T00:00:00Z","timestamp":1488499200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science and Technology (MOST) in Taiwan","award":["MOST 103-2314-B-010- 013-MY3 and MOST 104-2314-B-010-014-MY2"],"award-info":[{"award-number":["MOST 103-2314-B-010- 013-MY3 and MOST 104-2314-B-010-014-MY2"]}]},{"name":"Department of Health in Taipei City Government","award":["10501-62-050"],"award-info":[{"award-number":["10501-62-050"]}]},{"DOI":"10.13039\/100012553","name":"Chang Gung Memorial Hospital","doi-asserted-by":"publisher","award":["CMRPG8C1221, CMRPG8C1222, and CMRPG8C1223"],"award-info":[{"award-number":["CMRPG8C1221, CMRPG8C1222, and CMRPG8C1223"]}],"id":[{"id":"10.13039\/100012553","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>In addition to its well-established neurotrophic action, brain-derived neurotrophic factor (BDNF) also possesses other neuroprotective effects including anti-apoptosis, anti-oxidation, and suppression of autophagy. We have shown before that BDNF triggers multiple mechanisms to confer neuronal resistance against 3-nitropropionic acid (3-NP)-induced mitochondrial dysfunction in primary rat cortical cultures. The beneficial effects of BDNF involve the induction of anti-oxidative thioredoxin with the resultant expression of anti-apoptotic B-cell lymphoma 2 (Bcl-2) as well as erythropoietin (EPO)-dependent stimulation of sonic hedgehog (SHH). We further revealed that BDNF may bring the expression of sulfiredoxin, an ATP-dependent antioxidant enzyme, to offset mitochondrial inhibition in cortical neurons. Recently, we provided insights into another novel anti-oxidative mechanism of BDNF, which involves the augmentation of sestrin2 expression to endow neuronal resistance against oxidative stress induced by 3-NP; BDNF induction of sestrin2 entails the activation of a pathway involving nitric oxide (NO), cyclic guanosine monophosphate (cGMP)-dependent protein kinase (PKG), and nuclear factor-\u03baB (NF-\u03baB). Apart from anti-apoptosis and anti-oxidation, we demonstrated in our most recent study that BDNF may activate the mammalian target of rapamycin (mTOR) with resultant activation of transcription factor c-Jun, thereby stimulating the expression of p62\/sequestosome-1 to suppress heightened autophagy as a result of 3-NP exposure. Together, our results provide in-depth insight into multi-faceted protective mechanisms of BDNF against mitochondrial dysfunction commonly associated with the pathogenesis of many chronic neurodegenerative disorders. Delineation of the protective signaling pathways elicited by BDNF would endow a rationale to develop novel therapeutic regimens to halt or prevent the progression of neurodegeneration.<\/jats:p>","DOI":"10.3390\/ijms18030545","type":"journal-article","created":{"date-parts":[[2017,3,3]],"date-time":"2017-03-03T11:30:04Z","timestamp":1488540604000},"page":"545","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":206,"title":["More Insight into BDNF against Neurodegeneration: Anti-Apoptosis, Anti-Oxidation, and Suppression of Autophagy"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7879-2579","authenticated-orcid":false,"given":"Shang-Der","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Neurology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan"},{"name":"Institute for Translation Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83301, Taiwan"},{"name":"College of Medicine, Chang Gung University, Taoyuan 33302, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia-Lin","family":"Wu","sequence":"additional","affiliation":[{"name":"Program in Molecular Medicine, National Yang-Ming University and Academia Sinica, Taipei 11221, Taiwan"},{"name":"Institute of Brain Science and Brain Research Center, National Yang-Ming University, Taipei 11221, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei-Chao","family":"Hwang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Taipei City Hospital, Taipei 11221, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ding-I","family":"Yang","sequence":"additional","affiliation":[{"name":"Institute of Brain Science and Brain Research Center, National Yang-Ming University, Taipei 11221, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2017,3,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"12764","DOI":"10.1523\/JNEUROSCI.3566-09.2009","article-title":"New insights in the biology of BDNF synthesis and release: Implications in CNS function","volume":"29","author":"Greenberg","year":"2009","journal-title":"J. Neurosci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1038\/nrneurol.2009.54","article-title":"Brain-derived neurotrophic factor in neurodegenerative diseases","volume":"5","author":"Zuccato","year":"2009","journal-title":"Nat. Rev. Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1038\/nrn3505","article-title":"BDNF-based synaptic repair as a disease-modifying strategy for neurodegenerative diseases","volume":"14","author":"Lu","year":"2013","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1002\/ana.410300410","article-title":"Physical basis of cognitive alterations in Alzheimer\u2019s disease: Synapse loss is the major correlate of cognitive impairment","volume":"30","author":"Terry","year":"1991","journal-title":"Ann. Neurol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1016\/j.neuroscience.2005.01.007","article-title":"Evidence of a breakdown of corticostriatal connections in Parkinson\u2019s disease","volume":"132","author":"Stephens","year":"2005","journal-title":"Neuroscience"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1126\/science.3155875","article-title":"Evidence for degenerative and regenerative changes in neostriatal spiny neurons in Huntington\u2019s disease","volume":"227","author":"Graveland","year":"1985","journal-title":"Science"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1007\/s12035-012-8302-9","article-title":"Synaptic plasticity in neurodegenerative diseases evaluated and modulated by in vivo neurophysiological techniques","volume":"46","author":"Pilato","year":"2012","journal-title":"Mol. Neurobiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1275","DOI":"10.1089\/ars.2010.3359","article-title":"Calcium dysregulation and homeostasis of neural calcium in the molecular mechanisms of neurodegenerative diseases provide multiple targets for neuroprotection","volume":"14","author":"Zundorf","year":"2011","journal-title":"Antioxid. Redox Signal."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1385\/NMM:3:2:65","article-title":"Excitotoxic and excitoprotective mechanisms: Abundant targets for the prevention and treatment of neurodegenerative disorders","volume":"3","author":"Mattson","year":"2003","journal-title":"Neuromol. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"405194","DOI":"10.1155\/2011\/405194","article-title":"Protective action of neurotrophic factors and estrogen against oxidative stress-mediated neurodegeneration","volume":"2011","author":"Numakawa","year":"2011","journal-title":"J. Toxicol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"4094","DOI":"10.1007\/s12035-015-9337-5","article-title":"Oxidative stress in neurodegenerative diseases","volume":"53","author":"Niedzielska","year":"2015","journal-title":"Mol. Neurobiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"S18","DOI":"10.1038\/nrn1434","article-title":"Oxidative stress in neurodegeneration: Cause or consequence?","volume":"10","author":"Andersen","year":"2004","journal-title":"Nat. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1016\/j.pneurobio.2007.01.003","article-title":"Role of brain-derived neurotrophic factor in Huntington\u2019s disease","volume":"81","author":"Zuccato","year":"2007","journal-title":"Prog. Neurobiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"12748","DOI":"10.1523\/JNEUROSCI.3873-06.2006","article-title":"Mutant huntingtin impairs the post-Golgi trafficking of brain-derived neurotrophic factor but not its Val66Met polymorphism","volume":"26","author":"Canals","year":"2006","journal-title":"J. Neurosci."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3767","DOI":"10.1073\/pnas.74.9.3767","article-title":"3-Nitropropionate, the toxic substance of Indigofera, is a suicide inactivator of succinate dehydrogenase","volume":"74","author":"Alston","year":"1977","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"4181","DOI":"10.1523\/JNEUROSCI.13-10-04181.1993","article-title":"Neurochemical and histologic characterization of striatal excitotoxic lesions produced by the mitochondrial toxin 3-nitropropionic acid","volume":"13","author":"Beal","year":"1993","journal-title":"J. Neurosci."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1097\/00019052-199512000-00014","article-title":"Effects of chronic MPTP and 3-nitropropionic acid in nonhuman primates","volume":"8","author":"Brouillet","year":"1995","journal-title":"Curr. Opin. Neurol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"7105","DOI":"10.1073\/pnas.92.15.7105","article-title":"Chronic mitochondrial energy impairment produces selective striatal degeneration and abnormal choreiform movements in primates","volume":"92","author":"Brouillet","year":"1995","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1111\/j.1749-6632.2010.05628.x","article-title":"Neuroprotective mechanisms of brain-derived neurotrophic factor against 3-nitropropionic acid toxicity: Therapeutic implications for Huntington\u2019s disease","volume":"1201","author":"Wu","year":"2010","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"4126","DOI":"10.1007\/s12035-015-9357-1","article-title":"Nuclear factor-\u03baB-dependent sestrin2 induction mediates the antioxidant effects of BDNF against mitochondrial inhibition in rat cortical neurons","volume":"53","author":"Wu","year":"2016","journal-title":"Mol. Neurobiol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Wu, C.L., Chen, C.H., Hwang, C.S., Chen, S.D., Hwang, W.C., and Yang, D.I. (2016). Roles of p62 in BDNF-dependent autophagy suppression and neuroprotection against mitochondrial dysfunction in rat cortical neurons. J. Neurochem., in press.","DOI":"10.1111\/jnc.13937"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1693","DOI":"10.1212\/WNL.0000000000001507","article-title":"Brain-derived neurotrophic factor: Regulation, effects, and potential clinical relevance","volume":"84","author":"Benarroch","year":"2015","journal-title":"Neurology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1740","DOI":"10.1046\/j.1471-4159.1995.65041740.x","article-title":"Neurotrophic factors attenuate glutamate-induced accumulation of peroxides, elevation of intracellular Ca2+ concentration, and neurotoxicity and increase antioxidant enzyme activities in hippocampal neurons","volume":"65","author":"Mattson","year":"1995","journal-title":"J. Neurochem."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Tsai, C.Y., Chan, J.Y., Hsu, K.S., Chang, A.Y., and Chan, S.H. (2012). Brain-derived neurotrophic factor ameliorates brain stem cardiovascular dysregulation during experimental temporal lobe status epilepticus. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0033527"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1251","DOI":"10.1111\/j.1471-4159.2008.05864.x","article-title":"The CREB\/CRE transcriptional pathway: Protection against oxidative stress-mediated neuronal cell death","volume":"108","author":"Lee","year":"2009","journal-title":"J. Neurochem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.1161\/CIRCRESAHA.110.225573","article-title":"Transcriptional upregulation of brain-derived neurotrophic factor in rostral ventrolateral medulla by angiotensin II: Significance in superoxide homeostasis and neural regulation of arterial pressure","volume":"107","author":"Chan","year":"2010","journal-title":"Circ. Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1016\/j.nbd.2009.06.006","article-title":"BDNF regulates BIM expression levels in 3-nitropropionic acid-treated cortical neurons","volume":"35","author":"Almeida","year":"2009","journal-title":"Neurobiol. Dis."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1007\/s12640-009-9116-z","article-title":"Dysregulation of CREB activation and histone acetylation in 3-nitropropionic acid-treated cortical neurons: Prevention by BDNF and NGF","volume":"17","author":"Almeida","year":"2010","journal-title":"Neurotox. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.bbrc.2009.04.145","article-title":"Sonic hedgehog mediates BDNF-induced neuroprotection against mitochondrial inhibitor 3-nitropropionic acid","volume":"385","author":"Wu","year":"2009","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1016\/j.nbd.2010.05.019","article-title":"Erythropoietin and sonic hedgehog mediate the neuroprotective effects of brain-derived neurotrophic factor against mitochondrial inhibition","volume":"40","author":"Wu","year":"2010","journal-title":"Neurobiol. Dis."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1016\/j.neuro.2009.03.008","article-title":"Protective effects of brain-derived neurotrophic factor against neurotoxicity of 3-nitropropionic acid in rat cortical neurons","volume":"30","author":"Wu","year":"2009","journal-title":"Neurotoxicology"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1016\/j.nbd.2012.02.010","article-title":"c-Jun-dependent sulfiredoxin induction mediates BDNF protection against mitochondrial inhibition in rat cortical neurons","volume":"46","author":"Wu","year":"2012","journal-title":"Neurobiol. Dis."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2306","DOI":"10.1016\/j.bbamcr.2015.05.014","article-title":"Oncostatin M-dependent Mcl-1 induction mediated by JAK1\/2-STAT1\/3 and CREB contributes to bioenergetic improvements and protective effects against mitochondrial dysfunction in cortical neurons","volume":"1853","author":"Chang","year":"2015","journal-title":"Biochim. Biophys. Acta Mol. Cell Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1152\/physrev.1992.72.2.449","article-title":"Erythropoietin: Structure, control of production, and function","volume":"72","author":"Jelkmann","year":"1992","journal-title":"Physiol. Rev."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"3233","DOI":"10.1242\/jeb.01049","article-title":"Erythropoietin and the hypoxic brain","volume":"207","author":"Marti","year":"2004","journal-title":"J. Exp. Biol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"4044","DOI":"10.1073\/pnas.051606598","article-title":"Erythropoietin prevents neuronal apoptosis after cerebral ischemia and metabolic stress","volume":"98","author":"Siren","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"32462","DOI":"10.1074\/jbc.M706880200","article-title":"The Sonic hedgehog pathway mediates carbamylated erythropoietin-enhanced proliferation and differentiation of adult neural progenitor cells","volume":"282","author":"Wang","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.tem.2013.10.006","article-title":"BDNF mediates adaptive brain and body responses to energetic challenges","volume":"25","author":"Marosi","year":"2014","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/S0169-328X(02)00331-5","article-title":"Altered expression of novel genes in the cerebral cortex following experimental brain injury","volume":"104","author":"Kobori","year":"2002","journal-title":"Brain Res. Mol. Brain Res."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1016\/S0169-328X(02)00191-2","article-title":"Effect of ischemic preconditioning on the expression of putative neuroprotective genes in the rat brain","volume":"103","author":"Truettner","year":"2002","journal-title":"Brain Res. Mol. Brain Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"34419","DOI":"10.1074\/jbc.M110.126839","article-title":"Redox regulation of lipopolysaccharide-mediated sulfiredoxin induction, which depends on both AP-1 and Nrf2","volume":"285","author":"Kim","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"980","DOI":"10.1038\/nature02075","article-title":"ATP-dependent reduction of cysteine-sulphinic acid by S. cerevisiae sulphiredoxin","volume":"425","author":"Biteau","year":"2003","journal-title":"Nature"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"6017","DOI":"10.1038\/sj.onc.1205877","article-title":"Identification of a novel stress-responsive gene Hi95 involved in regulation of cell viability","volume":"21","author":"Budanov","year":"2002","journal-title":"Oncogene"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1679","DOI":"10.1089\/ars.2010.3530","article-title":"Stress-responsive sestrins link p53 with redox regulation and mammalian target of rapamycin signaling","volume":"15","author":"Budanov","year":"2011","journal-title":"Antioxid. Redox Signal."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1007\/s12031-013-0081-x","article-title":"Upregulation of sestrin-2 expression via p53 protects against 1-methyl-4-phenylpyridinium (MPP+) neurotoxicity","volume":"51","author":"Zhou","year":"2013","journal-title":"J. Mol. Neurosci."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.expneurol.2013.12.009","article-title":"Induction of sestrin2 as an endogenous protective mechanism against amyloid \u03b2-peptide neurotoxicity in primary cortical culture","volume":"253","author":"Chen","year":"2014","journal-title":"Exp. Neurol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"26406","DOI":"10.3390\/ijms161125963","article-title":"Roles of Sestrin2 and ribosomal protein S6 in transient global ischemia-induced hippocampal neuronal Injury","volume":"16","author":"Chuang","year":"2015","journal-title":"Int. J. Mol. Sci."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2013","DOI":"10.1089\/ars.2012.4958","article-title":"Antioxidant activity of sestrin2 controls neuropathic pain after peripheral nerve injury","volume":"19","author":"Lu","year":"2013","journal-title":"Antioxid. Redox Signal."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/nrm2822","article-title":"The nuts and bolts of AGC protein kinases","volume":"11","author":"Pearce","year":"2010","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1161\/01.RES.0000082524.34487.31","article-title":"Regulation of nitric oxide-sensitive guanylyl cyclase","volume":"93","author":"Friebe","year":"2003","journal-title":"Circ. Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1152\/physrev.00015.2005","article-title":"Function of cGMP-dependent protein kinases as revealed by gene deletion","volume":"86","author":"Hofmann","year":"2006","journal-title":"Physiol. Rev."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/j.cell.2008.06.028","article-title":"p53 target genes sestrin1 and sestrin2 connect genotoxic stress and mTOR signaling","volume":"134","author":"Budanov","year":"2008","journal-title":"Cell"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"3531","DOI":"10.1016\/j.febslet.2009.10.017","article-title":"Role of sestrin2 in peroxide signaling in macrophages","volume":"583","author":"Essler","year":"2009","journal-title":"FEBS Lett."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.freeradbiomed.2014.11.002","article-title":"Role of sestrin2 in the regulation of proinflammatory signaling in macrophages","volume":"78","author":"Yang","year":"2015","journal-title":"Free Radic. Biol. Med."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"834","DOI":"10.1016\/j.freeradbiomed.2012.06.026","article-title":"Nrf2-ARE pathway regulates induction of Sestrin-2 expression","volume":"53","author":"Shin","year":"2012","journal-title":"Free Radic. Biol. Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1111\/j.1600-065X.2008.00725.x","article-title":"Autophagy and pattern recognition receptors in innate immunity","volume":"227","author":"Delgado","year":"2009","journal-title":"Immunol. Rev."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1992","DOI":"10.1091\/mbc.e08-12-1249","article-title":"ULK-Atg13-FIP200 complexes mediate mTOR signaling to the autophagy machinery","volume":"20","author":"Jung","year":"2009","journal-title":"Mol. Biol. Cell"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2524","DOI":"10.4161\/cc.25835","article-title":"mTOR, AMBRA1, and autophagy: An intricate relationship","volume":"12","author":"Nazio","year":"2013","journal-title":"Cell Cycle"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1016\/j.ceb.2009.11.014","article-title":"Mammalian autophagy: Core molecular machinery and signaling regulation","volume":"22","author":"Yang","year":"2010","journal-title":"Curr. Opin. Cell Biol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1038\/ncb0910-836","article-title":"Selective autophagy: Ubiquitin-mediated recognition and beyond","volume":"12","author":"Kraft","year":"2010","journal-title":"Nat. Cell Biol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1016\/j.cellsig.2012.01.020","article-title":"Autophagy in regulation of Toll-like receptor signaling","volume":"24","author":"Into","year":"2012","journal-title":"Cell. Signal."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1374","DOI":"10.1016\/j.febslet.2010.02.017","article-title":"Physiological significance of selective degradation of p62 by autophagy","volume":"584","author":"Komatsu","year":"2010","journal-title":"FEBS Lett."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"24131","DOI":"10.1074\/jbc.M702824200","article-title":"p62\/SQSTM1 binds directly to Atg8\/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy","volume":"282","author":"Pankiv","year":"2007","journal-title":"J. Biol. Chem."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"3600","DOI":"10.1002\/jnr.22152","article-title":"Down-regulation of Bcl-2 enhances autophagy activation and cell death induced by mitochondrial dysfunction in rat striatum","volume":"87","author":"Zhang","year":"2009","journal-title":"J. Neurosci. Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1111\/j.1476-5381.2012.01994.x","article-title":"3-Nitropropionic acid induces autophagy by forming mitochondrial permeability transition pores rather than activating the mitochondrial fission pathway","volume":"168","author":"Solesio","year":"2013","journal-title":"Br. J. Pharmacol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.nbd.2010.01.013","article-title":"Sildenafil protects against 3-nitropropionic acid neurotoxicity through the modulation of calpain, CREB, and BDNF","volume":"38","author":"Puerta","year":"2010","journal-title":"Neurobiol. Dis."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1016\/j.bbrc.2015.08.075","article-title":"Differential caspase activity in the cortex and striatum with chronic infusion of 3-nitropropionic acid","volume":"465","author":"Cho","year":"2015","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.biopha.2016.11.111","article-title":"Effect of Praeruptorin C on 3-nitropropionic acid induced Huntington\u2019s disease-like symptoms in mice","volume":"86","author":"Wang","year":"2017","journal-title":"Biomed. Pharmacother."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.neulet.2014.11.036","article-title":"Memantine exerts functional recovery by improving BDNF and GDNF expression in 3-nitropropionic acid intoxicated mice","volume":"586","author":"Ranju","year":"2015","journal-title":"Neurosci. Lett."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1007\/s13311-014-0304-z","article-title":"Neuroprotective properties of cannabigerol in Huntington\u2019s disease: Studies in R6\/2 mice and 3-nitropropionate-lesioned mice","volume":"12","author":"Valdeolivas","year":"2015","journal-title":"Neurotherapeutics"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.nbd.2004.01.016","article-title":"Proactive transplantation of human neural stem cells prevents degeneration of striatal neurons in a rat model of Huntington disease","volume":"16","author":"Ryu","year":"2004","journal-title":"Neurobiol. Dis."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/j.bbr.2010.11.006","article-title":"Mesenchymal stem cell transplantation and DMEM administration in a 3-NP rat model of Huntington\u2019s disease: Morphological and behavioral outcomes","volume":"217","author":"Rossignol","year":"2011","journal-title":"Behav. 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