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

Authors

Timothy J. Collier, Department of Translational Science & Molecular Medicine, Michigan State UniversityGrand Rapids, MI, USA; Hauenstein Neuroscience Center, Mercy Health Saint Mary'sGrand Rapids, MI, USA.
D Eugene Redmond, Departments of Psychiatry & Neurosurgery, Yale University School of MedicineNew Haven, CT, USA; Axion Research FoundationHamden, CT, USA.
Kathy Steece-Collier, Department of Translational Science & Molecular Medicine, Michigan State UniversityGrand Rapids, MI, USA; Hauenstein Neuroscience Center, Mercy Health Saint Mary'sGrand Rapids, MI, USA.
Jack W. Lipton, Department of Translational Science & Molecular Medicine, Michigan State UniversityGrand Rapids, MI, USA; Hauenstein Neuroscience Center, Mercy Health Saint Mary'sGrand Rapids, MI, USA.
Fredric P. Manfredsson, Department of Translational Science & Molecular Medicine, Michigan State UniversityGrand Rapids, MI, USA; Hauenstein Neuroscience Center, Mercy Health Saint Mary'sGrand Rapids, MI, USA.Follow

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

Recommended Citation

Collier, Timothy J.; Redmond, D Eugene; Steece-Collier, Kathy; Lipton, Jack W.; and Manfredsson, Fredric P., "Is Alpha-Synuclein Loss-of-Function a Contributor to Parkinsonian Pathology? Evidence from Non-human Primates" (2016). Translational Neuroscience. 1431.
https://scholar.barrowneuro.org/neurobiology/1431