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Mitochondrial dysfunction in Parkinson's disease.
J Alzheimers Dis. 2010; 20 Suppl 2:S325-34.JA

Abstract

It is clear from a striking convergence of human tissue studies, neurotoxin models, and genetic models that mitochondrial dysregulation plays a central pathogenic role in Parkinson's disease (PD) and related neurodegenerative conditions. Impaired mitochondrial quality could result from both increased damage and decreased ability to repair or clear damaged mitochondria. In particular, common deficits in mitochondrial respiratory chain function, oxidative stress, morphology/dynamics, and calcium handling capacities have been described in multiple PD model systems employing complex I inhibitors, 6-hydroxydopamine and molecular manipulation of Parkinsonian genes including alpha-synuclein, PTEN-induced kinase 1, Parkin, DJ-1, and, to a lesser extent, leucine rich repeat kinase 2. The most recent and exciting work implicates alterations in the regulation of macroautophagy and likely of selective mitophagic clearance of damaged mitochondria, although additional studies are needed to resolve some issues in this area. Future studies emphasizing the normal mitoprotective function(s) of proteins associated with recessive loss-of-function causes of familial PD, as well as compensatory mechanisms operating in their absence, may offer particularly valuable insights into strategies to enhance mitochondrial health.

Authors+Show Affiliations

Department of Pathology (Division of Neuropathology), University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.No affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

20442495

Citation

Zhu, Jianhui, and Charleen T. Chu. "Mitochondrial Dysfunction in Parkinson's Disease." Journal of Alzheimer's Disease : JAD, vol. 20 Suppl 2, 2010, pp. S325-34.
Zhu J, Chu CT. Mitochondrial dysfunction in Parkinson's disease. J Alzheimers Dis. 2010;20 Suppl 2:S325-34.
Zhu, J., & Chu, C. T. (2010). Mitochondrial dysfunction in Parkinson's disease. Journal of Alzheimer's Disease : JAD, 20 Suppl 2, S325-34. https://doi.org/10.3233/JAD-2010-100363
Zhu J, Chu CT. Mitochondrial Dysfunction in Parkinson's Disease. J Alzheimers Dis. 2010;20 Suppl 2:S325-34. PubMed PMID: 20442495.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mitochondrial dysfunction in Parkinson's disease. AU - Zhu,Jianhui, AU - Chu,Charleen T, PY - 2010/5/6/entrez PY - 2010/5/6/pubmed PY - 2010/9/14/medline SP - S325 EP - 34 JF - Journal of Alzheimer's disease : JAD JO - J Alzheimers Dis VL - 20 Suppl 2 N2 - It is clear from a striking convergence of human tissue studies, neurotoxin models, and genetic models that mitochondrial dysregulation plays a central pathogenic role in Parkinson's disease (PD) and related neurodegenerative conditions. Impaired mitochondrial quality could result from both increased damage and decreased ability to repair or clear damaged mitochondria. In particular, common deficits in mitochondrial respiratory chain function, oxidative stress, morphology/dynamics, and calcium handling capacities have been described in multiple PD model systems employing complex I inhibitors, 6-hydroxydopamine and molecular manipulation of Parkinsonian genes including alpha-synuclein, PTEN-induced kinase 1, Parkin, DJ-1, and, to a lesser extent, leucine rich repeat kinase 2. The most recent and exciting work implicates alterations in the regulation of macroautophagy and likely of selective mitophagic clearance of damaged mitochondria, although additional studies are needed to resolve some issues in this area. Future studies emphasizing the normal mitoprotective function(s) of proteins associated with recessive loss-of-function causes of familial PD, as well as compensatory mechanisms operating in their absence, may offer particularly valuable insights into strategies to enhance mitochondrial health. SN - 1875-8908 UR - https://www.unboundmedicine.com/medline/citation/20442495/Mitochondrial_dysfunction_in_Parkinson's_disease_ L2 - https://content.iospress.com/openurl?genre=article&id=doi:10.3233/JAD-2010-100363 DB - PRIME DP - Unbound Medicine ER -