An Emerging Role for Phosphoinositides in the Pathophysiology of Parkinson’s Disease

Author:

Schechter Meir1,Sharon Ronit1

Affiliation:

1. Department of Biochemistry and Molecular Biology, IMRIC, The Hebrew University-Hadassah Medical School, Ein Kerem, Jerusalem, Israel

Abstract

Recent data support an involvement of defects in homeostasis of phosphoinositides (PIPs) in the pathophysiology of Parkinson’s disease (PD). Genetic mutations have been identified in genes encoding for PIP-regulating and PIP-interacting proteins, that are associated with familial and sporadic PD. Many of these proteins are implicated in vesicular membrane trafficking, mechanisms that were recently highlighted for their close associations with PD. PIPs are phosphorylated forms of the membrane phospholipid, phosphatidylinositol. Their composition in the vesicle’s membrane of origin, as well as membrane of destination, controls vesicular membrane trafficking. We review the converging evidence that points to the involvement of PIPs in PD. The review describes PD- and PIP-associated proteins implicated in clathrin-mediated endocytosis and autophagy, and highlights the involvement of α-synuclein in these mechanisms.

Publisher

IOS Press

Subject

Cellular and Molecular Neuroscience,Neurology (clinical)

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