Title

Is Alpha-Synuclein Loss-of-Function a Contributor to Parkinsonian Pathology? Evidence from Non-human Primates

Document Type

Article

Abstract

Accumulation of alpha-synuclein (α-syn) in Lewy bodies and neurites of midbrain dopamine neurons is diagnostic for Parkinson's disease (PD), leading to the proposal that PD is a toxic gain-of-function synucleinopathy. Here we discuss the alternative viewpoint that α-syn displacement from synapses by misfolding and aggregation results in a toxic loss-of-function. In support of this hypothesis we provide evidence from our pilot study demonstrating that knockdown of endogenous α-syn in dopamine neurons of non-human primates reproduces the pattern of nigrostriatal degeneration characteristic of PD.

Keywords

Parkinson's disease, alpha-synuclein, dopamine, non-human primates, substantia nigra

Publication Date

1-1-2016

Publication Title

Frontiers in neuroscience

ISSN

1662-4548

Volume

10

First Page

12

PubMed ID

26858591

Digital Object Identifier (DOI)

10.3389/fnins.2016.00012

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