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Autophagy. 2015;11(9):1443-57. doi: 10.1080/15548627.2015.1067364.

Genetic perspective on the role of the autophagy-lysosome pathway in Parkinson disease.

Gan-Or Z1,2, Dion PA1,2,3, Rouleau GA1,2,3.

Author information

1
a The Department of Human Genetics ; McGill University ; Montreal , QC Canada.
2
b Montreal Neurological Institute; McGill University ; Montreal , QC Canada.
3
c The Department of Neurology & Neurosurgery ; McGill University ; Montreal , QC Canada.

Abstract

Parkinson disease (PD), once considered as a prototype of a sporadic disease, is now known to be considerably affected by various genetic factors, which interact with environmental factors and the normal process of aging, leading to PD. Large studies determined that the hereditary component of PD is at least 27%, and in some populations, single genetic factors are responsible for more than 33% of PD patients. Interestingly, many of these genetic factors, such as LRRK2, GBA, SMPD1, SNCA, PARK2, PINK1, PARK7, SCARB2, and others, are involved in the autophagy-lysosome pathway (ALP). Some of these genes encode lysosomal enzymes, whereas others correspond to proteins that are involved in transport to the lysosome, mitophagy, or other autophagic-related functions. Is it possible that all these factors converge into a single pathway that causes PD? In this review, we will discuss these genetic findings and the role of the ALP in the pathogenesis of PD and will try to answer this question. We will suggest a novel hypothesis for the pathogenic mechanism of PD that involves the lysosome and the different autophagy pathways.

KEYWORDS:

GBA; LAMP2A; LRRK2; Parkinson disease; SNCA; autophagy; genetics; lysosome; mitophagy

PMID:
26207393
PMCID:
PMC4590678
DOI:
10.1080/15548627.2015.1067364
[Indexed for MEDLINE]
Free PMC Article

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