{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T22:54:04Z","timestamp":1770332044891,"version":"3.49.0"},"reference-count":36,"publisher":"Springer Science and Business Media LLC","issue":"8","license":[{"start":{"date-parts":[[2008,7,11]],"date-time":"2008-07-11T00:00:00Z","timestamp":1215734400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Neurol"],"published-print":{"date-parts":[[2008,8]]},"DOI":"10.1007\/s00415-008-0892-9","type":"journal-article","created":{"date-parts":[[2008,7,4]],"date-time":"2008-07-04T09:23:20Z","timestamp":1215163400000},"page":"1231-1235","source":"Crossref","is-referenced-by-count":67,"title":["Dopaminergic midbrain neurons are the prime target for mitochondrial DNA deletions"],"prefix":"10.1007","volume":"255","author":[{"given":"A.","family":"Bender","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R.-M.","family":"Schwarzkopf","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"McMillan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K. J.","family":"Krishnan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G.","family":"Rieder","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Neumann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Elstner","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D. M.","family":"Turnbull","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T.","family":"Klopstock","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2008,7,11]]},"reference":[{"key":"892_CR1","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1083\/jcb.200207030","volume":"161","author":"Anandatheerthavarada","year":"2003","unstructured":"Anandatheerthavarada HK, Biswas G, Robin MA, Avadhani NG (2003) Mitochondrial targeting and a novel transmembrane arrest of Alzheimer\u2019s amyloid precursor protein impairs mitochondrial function in neuronal cells. J Cell Biol 161:41\u201354","journal-title":"J Cell Biol"},{"key":"892_CR2","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/j.mito.2007.06.001","volume":"7","author":"Atamna","year":"2007","unstructured":"Atamna H, Frey WH 2nd (2007) Mechanisms of mitochondrial dysfunction and energy deficiency in Alzheimer\u2019s disease. Mitochondrion 7:297\u2013310","journal-title":"Mitochondrion"},{"key":"892_CR3","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1038\/ng1769","volume":"38","author":"Bender","year":"2006","unstructured":"Bender A, Krishnan KJ, Morris CM, Taylor GA, Reeve AK, Perry RH, Jaros E, Hersheson JS, Betts J, Klopstock T, Taylor RW, Turnbull DM (2006) High levels of mitochondrial DNA deletions in substantia nigra neurons in aging and Parkinson disease. Nat Genet 38:515\u2013517","journal-title":"Nat Genet"},{"key":"892_CR4","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1038\/81834","volume":"3","author":"Betarbet","year":"2000","unstructured":"Betarbet R, Sherer TB, MacKenzie G, Garcia-Osuna M, Panov AV, Greenamyre JT (2000) Chronic systemic pesticide exposure reproduces features of Parkinson\u2018s disease. Nat Neurosci 3:1301\u20131306","journal-title":"Nat Neurosci"},{"key":"892_CR5","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1023\/B:NERE.0000014821.07269.8d","volume":"29","author":"Betts","year":"2004","unstructured":"Betts J, Lightowlers RN, Turnbull DM (2004) Neuropathological aspects of mitochondrial DNA disease. Neurochem Res 29:505\u2013511","journal-title":"Neurochem Res"},{"key":"892_CR6","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1080\/15216540051080912","volume":"50","author":"Boveris","year":"2000","unstructured":"Boveris A, Cadenas E (2000) Mitochondrial production of hydrogen peroxide: regulation by nitric oxide and the role of ubisemiquinone. IUBMB Life 50:245\u2013250","journal-title":"IUBMB Life"},{"key":"892_CR7","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1007\/BF00308809","volume":"82","author":"Braak","year":"1991","unstructured":"Braak H, Braak E (1991) Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol 82:239\u2013259","journal-title":"Acta Neuropathol"},{"key":"892_CR8","doi-asserted-by":"crossref","first-page":"4890","DOI":"10.1073\/pnas.94.10.4890","volume":"94","author":"Cohen","year":"1997","unstructured":"Cohen G, Farooqui R, Kesler N (1997) Parkinson disease: a new link between monoamine oxidase and mitochondrial electron flow. Proc Natl Acad Sci U S A 94:4890\u20134894","journal-title":"Proc Natl Acad Sci U S A"},{"key":"892_CR9","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1006\/geno.1994.1525","volume":"23","author":"Corral-Debrinski","year":"1994","unstructured":"Corral-Debrinski M, Horton T, Lott MT, Shoffner JM, McKee AC, Beal MF, Graham BH, Wallace DC (1994) Marked changes in mitochondrial DNA deletion levels in Alzheimer brains. Genomics 23:471\u2013476","journal-title":"Genomics"},{"key":"892_CR10","doi-asserted-by":"crossref","first-page":"10726","DOI":"10.1073\/pnas.0403649101","volume":"101","author":"Coskun","year":"2004","unstructured":"Coskun PE, Beal MF, Wallace DC (2004) Alzheimer\u2018s brains harbor somatic mtDNA control-region mutations that suppress mitochondrial transcription and replication. Proc Natl Acad Sci U S A 101:10726\u201310731","journal-title":"Proc Natl Acad Sci U S A"},{"key":"892_CR11","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1111\/j.1749-6632.2000.tb06647.x","volume":"908","author":"Cottrell","year":"2000","unstructured":"Cottrell DA, Blakely EL, Borthwick GM, Johnson MA, Taylor GA, Brierley EJ, Ince PG, Turnbull DM (2000) Role of mitochondrial DNA mutations in disease and aging. Ann N Y Acad Sci 908:199\u2013207","journal-title":"Ann N Y Acad Sci"},{"key":"892_CR12","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1212\/WNL.57.2.260","volume":"57","author":"Cottrell","year":"2001","unstructured":"Cottrell DA, Blakely EL, Johnson MA, Ince PG, Turnbull DM (2001) Mitochondrial enzyme-deficient hippocampal neurons and choroidal cells in AD. Neurology 57:260\u2013264","journal-title":"Neurology"},{"key":"892_CR13","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1046\/j.1365-2990.2002.00414.x","volume":"28","author":"Cottrell","year":"2002","unstructured":"Cottrell DA, Borthwick GM, Johnson MA, Ince PG, Turnbull DM (2002) The role of cytochrome c oxidase deficient hippocampal neurones in Alzheimer\u2018s disease. Neuropathol Appl Neurobiol 28:390\u2013396","journal-title":"Neuropathol Appl Neurobiol"},{"key":"892_CR14","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.conb.2007.04.010","volume":"17","author":"Dodson","year":"2007","unstructured":"Dodson MW, Guo M (2007) Pink1, Parkin, DJ-1 and mitochondrial dysfunction in Parkinson\u2018s disease. Curr Opin Neurobiol 17:331\u2013337","journal-title":"Curr Opin Neurobiol"},{"key":"892_CR15","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1111\/j.1471-4159.2005.03638.x","volume":"96","author":"Fasano","year":"2006","unstructured":"Fasano M, Bergamasco B, Lopiano L (2006) Modifications of the iron-neuromelanin system in Parkinson\u2018s disease. J Neurochem 96:909\u2013916","journal-title":"J Neurochem"},{"key":"892_CR16","doi-asserted-by":"crossref","first-page":"3413","DOI":"10.1073\/pnas.0409713102","volume":"102","author":"Fornai","year":"2005","unstructured":"Fornai F, Schluter OM, Lenzi P, Gesi M, Ruffoli R, Ferrucci M, Lazzeri G, Busceti CL, Pontarelli F, Battaglia G, Pellegrini A, Nicoletti F, Ruggieri S, Paparelli A, Sudhof TC (2005) Parkinson-like syndrome induced by continuous MPTP infusion: convergent roles of the ubiquitin-proteasome system and alpha-synuclein. Proc Natl Acad Sci U S A 102:3413\u20133418","journal-title":"Proc Natl Acad Sci U S A"},{"key":"892_CR17","doi-asserted-by":"crossref","first-page":"14163","DOI":"10.1073\/pnas.0705738104","volume":"104","author":"Fukui","year":"2007","unstructured":"Fukui H, Diaz F, Garcia S, Moraes CT (2007) Cytochrome c oxidase deficiency in neurons decreases both oxidative stress and amyloid formation in a mouse model of Alzheimer\u2018s disease. Proc Natl Acad Sci U S A 104:14163\u201314168","journal-title":"Proc Natl Acad Sci U S A"},{"key":"892_CR18","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1046\/j.1471-4159.2002.00938.x","volume":"82","author":"Gluck","year":"2002","unstructured":"Gluck M, Ehrhart J, Jayatilleke E, Zeevalk GD (2002) Inhibition of brain mitochondrial respiration by dopamine: involvement of H(2)O(2) and hydroxyl radicals but not glutathione-proteinmixed disulfides. J Neurochem 82:66\u201374","journal-title":"J Neurochem"},{"key":"892_CR19","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.nbd.2004.10.003","volume":"18","author":"Greene","year":"2005","unstructured":"Greene JG, Dingledine R, Greenamyre JT (2005) Gene expression profiling of rat midbrain dopamine neurons: implications for selective vulnerability in parkinsonism. Neurobiol Dis 18:19\u201331","journal-title":"Neurobiol Dis"},{"key":"892_CR20","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/S0027-5107(97)00158-9","volume":"379","author":"Hamblet","year":"1997","unstructured":"Hamblet NS, Castora FJ (1997) Elevated levels of the Kearns-Sayre syndrome mitochondrial DNA deletion in temporal cortex of Alzheimer\u2019s patients. Mutat Res 379:253\u2013262","journal-title":"Mutat Res"},{"key":"892_CR21","doi-asserted-by":"crossref","first-page":"668","DOI":"10.1016\/j.exger.2006.03.012","volume":"41","author":"Hauptmann","year":"2006","unstructured":"Hauptmann S, Keil U, Scherping I, Bonert A, Eckert A, Muller WE (2006) Mitochondrial dysfunction in sporadic and genetic Alzheimer\u2019s disease. Exp Gerontol 41:668\u2013673","journal-title":"Exp Gerontol"},{"key":"892_CR22","doi-asserted-by":"crossref","first-page":"e68","DOI":"10.1093\/nar\/gnf067","volume":"30","author":"He","year":"2002","unstructured":"He L, Chinnery PF, Durham SE, Blakely EL, Wardell TM, Borthwick GM, Taylor RW, Turnbull DM (2002) Detection and quantification of mitochondrial DNA deletions in individual cells by real-time PCR. Nucleic Acids Res 30:e68","journal-title":"Nucleic Acids Res"},{"key":"892_CR23","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1038\/334345a0","volume":"334","author":"Hirsch","year":"1988","unstructured":"Hirsch E, Graybiel AM, Agid YA (1988) Melanized dopaminergic neurons are differentially susceptible to degeneration in Parkinson\u2018s disease. Nature 334:345\u2013348","journal-title":"Nature"},{"key":"892_CR24","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.bbadis.2005.03.013","volume":"1741","author":"Khan","year":"2005","unstructured":"Khan FH, Sen T, Maiti AK, Jana S, Chatterjee U, Chakrabarti S (2005) Inhibition of rat brain mitochondrial electron transport chain activity by dopamine oxidation products during extended in vitro incubation: implications for Parkinson\u2018s disease. Biochim Biophys Acta 1741:65\u201374","journal-title":"Biochim Biophys Acta"},{"key":"892_CR25","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.ab.2007.06.024","volume":"370","author":"Krishnan","year":"2007","unstructured":"Krishnan KJ, Bender A, Taylor RW, Turnbull DM (2007). A multiplex realtime PCR method to detect and quantify mitochondrial DNA deletions in individual cells. Anal Biochem 370:127\u2013129","journal-title":"Anal Biochem"},{"key":"892_CR26","doi-asserted-by":"crossref","first-page":"7399","DOI":"10.1093\/nar\/gkm635","volume":"35","author":"Krishnan","year":"2007","unstructured":"Krishnan KJ, Greaves LC, Reeve AK, Turnbull D (2007) The ageing mitochondrial genome. Nucleic Acids Res 35:7399\u20137405","journal-title":"Nucleic Acids Res"},{"key":"892_CR27","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1038\/nature05292","volume":"443","author":"Lin","year":"2006","unstructured":"Lin MT, Beal MF (2006) Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. Nature 443:787\u2013795","journal-title":"Nature"},{"key":"892_CR28","doi-asserted-by":"crossref","first-page":"448","DOI":"10.1126\/science.1091230","volume":"304","author":"Lustbader","year":"2004","unstructured":"Lustbader JW, Cirilli M, Lin C, Xu HW, Takuma K, Wang N, Caspersen C, Chen X, Pollak S, Chaney M, Trinchese F, Liu S, Gunn-Moore F, Lue LF, Walker DG, Kuppusamy P, Zewier ZL, Arancio O, Stern D, Yan SS, Wu H (2004) ABAD directly links Abeta to mitochondrial toxicity in Alzheimer\u2018s disease. Science 304:448\u2013452","journal-title":"Science"},{"key":"892_CR29","doi-asserted-by":"crossref","first-page":"1437","DOI":"10.1093\/hmg\/ddl066","volume":"15","author":"Manczak","year":"2006","unstructured":"Manczak M, Anekonda TS, Henson E, Park BS, Quinn J, Reddy PH (2006) Mitochondria are a direct site of A beta accumulation in Alzheimer\u2018s disease neurons: implications for free radical generation and oxidative damage in disease progression. Hum Mol Genet 15:1437\u20131449","journal-title":"Hum Mol Genet"},{"key":"892_CR30","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1385\/NMM:5:2:147","volume":"5","author":"Manczak","year":"2004","unstructured":"Manczak M, Park BS, Jung Y, Reddy PH (2004) Differential expression of oxidative phosphorylation genes in patients with Alzheimer\u2018s disease: implications for early mitochondrial dysfunction and oxidative damage. Neuromolecular Med 5:147\u2013162","journal-title":"Neuromolecular Med"},{"key":"892_CR31","doi-asserted-by":"crossref","first-page":"49064","DOI":"10.1074\/jbc.M407715200","volume":"279","author":"Muller","year":"2004","unstructured":"Muller FL, Liu Y, Van Remmen H (2004) Complex III releases superoxide to both sides of the inner mitochondrial membrane. J Biol Chem 279:49064\u201349073","journal-title":"J Biol Chem"},{"key":"892_CR32","doi-asserted-by":"crossref","first-page":"1647","DOI":"10.1089\/ars.2007.1754","volume":"9","author":"Reddy","year":"2007","unstructured":"Reddy PH (2007) Mitochondrial dysfunction in aging and Alzheimer\u2018s disease: strategies to protect neurons. Antioxid Redox Signal 9:1647\u20131658","journal-title":"Antioxid Redox Signal"},{"key":"892_CR33","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1016\/S0140-6736(89)92366-0","volume":"1","author":"Schapira","year":"1989","unstructured":"Schapira AH, Cooper JM, Dexter D, Jenner P, Clark JB, Marsden CD (1989) Mitochondrial complex I deficiency in Parkinson\u2018s disease. Lancet 1(8649):1269","journal-title":"Lancet"},{"key":"892_CR34","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1093\/hmg\/3.1.13","volume":"3","author":"Sciacco","year":"1994","unstructured":"Sciacco M, Bonilla E, Schon EA, Di- Mauro S, Moraes CT (1994) Distribution of wild-type and common deletion forms of mtDNA in normal and respiration-deficient muscle fibers from patients with mitochondrial myopathy. Hum Mol Genet 3:13\u201319 Neuropharmacology 40:927\u2013936","journal-title":"Hum Mol Genet"},{"key":"892_CR35","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1007\/s00702-005-0410-5","volume":"113","author":"Shamoto-Nagai","year":"2006","unstructured":"Shamoto-Nagai M, Maruyama W, Yi H, Akao Y, Tribl F, Gerlach M, Osawa T, Riederer P, Naoi M (2006) Neuromelanin induces oxidative stress in mitochondria through release of iron: mechanism behind the inhibition of 26S proteasome. J Neural Transm 113:633\u2013644","journal-title":"J Neural Transm"},{"key":"892_CR36","doi-asserted-by":"crossref","unstructured":"Werkman TR, Kruse CG, Nievelstein H, Long SK, Wadman WJ (2001) In vitro modulation of the firing rate of dopamine neurons in the rat substantia nigra pars compacta and the ventral tegmental area by antipsychotic drugs.","DOI":"10.1016\/S0028-3908(01)00015-6"}],"container-title":["Journal of Neurology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00415-008-0892-9.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s00415-008-0892-9\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s00415-008-0892-9","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,5,28]],"date-time":"2019-05-28T19:08:16Z","timestamp":1559070496000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s00415-008-0892-9"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2008,7,11]]},"references-count":36,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2008,8]]}},"alternative-id":["892"],"URL":"https:\/\/doi.org\/10.1007\/s00415-008-0892-9","relation":{},"ISSN":["0340-5354","1432-1459"],"issn-type":[{"value":"0340-5354","type":"print"},{"value":"1432-1459","type":"electronic"}],"subject":[],"published":{"date-parts":[[2008,7,11]]}}}