Abstract
Parkinson's disease is a debilitating, age-associated movement disorder. A central aspect of the pathophysiology of Parkinson's disease is the progressive demise of midbrain dopamine neurons and their axonal projections, but the underlying causes of this loss are unclear. Advances in genetics and experimental model systems have illuminated an important role for defects in intracellular transport pathways to lysosomes. The accumulation of altered proteins and damaged mitochondria, particularly at axon terminals, ultimately might overwhelm the capacity of intracellular disposal mechanisms. Cell-extrinsic mechanisms, including inflammation and prion-like spreading, are proposed to have both protective and deleterious functions in Parkinson's disease.
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We would like to thank S. Pfeffer for reading the manuscript. This work was funded by grants from the Michael J. Fox Foundation and the US National Institute of Neurological Disorders and Stroke.
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A.A. is a co-founder of and a consultant to Alector Inc., a biotechnology company.
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Abeliovich, A., Gitler, A. Defects in trafficking bridge Parkinson's disease pathology and genetics. Nature 539, 207–216 (2016). https://doi.org/10.1038/nature20414
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DOI: https://doi.org/10.1038/nature20414
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