Loss of Parkin contributes to mitochondrial turnover and dopaminergic neuronal loss in aged mice.

Autor: Noda S; Department of Neurology, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan., Sato S; Department of Neurology, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan., Fukuda T; Division of Neuropathology, Department of Neuropathology, The Jikei University, School of Medicine, Tokyo 105-8461, Japan., Tada N; Atopy Research Center, Juntendo University School of Medicine, Tokyo 113-8421, Japan., Uchiyama Y; Department of Cellular and Molecular Neuropathology, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan., Tanaka K; Laboratory of Protein Metabolism, Metropolitan Institute of Medical Science, Tokyo, Japan., Hattori N; Department of Neurology, Juntendo University Graduate School of Medicine, Tokyo 113-8421, Japan. Electronic address: s-sato@juntendo.ac.jp.
Jazyk: angličtina
Zdroj: Neurobiology of disease [Neurobiol Dis] 2020 Mar; Vol. 136, pp. 104717. Date of Electronic Publication: 2019 Dec 15.
DOI: 10.1016/j.nbd.2019.104717
Abstrakt: Parkinson's disease (PD), the second most common neurodegenerative disorder, is characterized by the loss of nigrostriatal dopamine neurons. PARK2 mutations cause early-onset Parkinson's disease (EO-PD). PARK2 encodes an E3 ubiquitin ligase, Parkin. Extensive in vitro studies and cell line characterization have shown that Parkin is required for mitophagy, but the physiological pathology and context of the pathway remain unknown. In general, monogenic Parkin knockout mice do not accurately reflect human PD symptoms and exhibit no signs of dopaminergic (DA) neurodegeneration. To assess the critical role of Parkin-mediated mitophagy in DA neurons, we characterized Parkin knockout mice over a long period of time. At the age of 110 weeks, Parkin knockout mice exhibited locomotor impairments, including hindlimb defects and neuronal loss. In their DA neurons, fragmented mitochondria with abnormal internal structures accumulated. The age-related motor dysfunction and damaged mitochondria pathology in Parkin-deficient mice suggest that impairment of mitochondrial clearance may underlie the pathology of PD.
Competing Interests: Declaration of Competing Interest The author declares no conflicts of interest.
(Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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