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Mov Disord. 2016 Oct;31(10):1433-1443. doi: 10.1002/mds.26797.

Endolysosomal dysfunction in Parkinson's disease: Recent developments and future challenges.

Author information

1
Department of Neurology, University of Michigan Medical School, Ann Arbor, Michigan, USA.
2
Medical Scientist Training Program, University of Michigan Medical School, Ann Arbor, Michigan, USA.
3
Department of Neurology, University of Michigan Medical School, Ann Arbor, Michigan, USA. dauer@med.umich.edu.
4
Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, Michigan, USA. dauer@med.umich.edu.

Abstract

Increasingly, genetic, cell biological, and in vivo work emphasizes the role of the endolysosomal system dysfunction in Parkinson's disease pathogenesis. Yet many questions remain about the mechanisms by which primary endolysosomal dysfunction causes PD as well as how the endolysosomal system interacts with α-synuclein-mediated neurotoxicity. We recently described a new mouse model of parkinsonism in which loss of the endolysosomal protein Atp13a2 causes behavioral, neuropathological, and biochemical changes similar to those present in human subjects with ATP13A2 mutations. In this Scientific Perspectives, we revisit the evidence implicating the endolysosomal system in PD, current hypotheses of disease pathogenesis, and how recent studies refine these hypotheses and raise new questions for future research.

KEYWORDS:

Atp13a2; Kufor-Rakeb syndrome; Parkinson's disease; endolysosomal system

PMID:
27619535
PMCID:
PMC5061051
DOI:
10.1002/mds.26797
[Indexed for MEDLINE]
Free PMC Article

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