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Review
. 2021;11(4):1725-1750.
doi: 10.3233/JPD-212684.

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

Meir Schechter  1 , Ronit Sharon  1
Affiliations
Review

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

Meir Schechter et al. J Parkinsons Dis. 2021.

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.

Keywords: Parkinson’s disease; phosphoinositides; vesicular membrane trafficking.

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Conflict of interest statement

The authors have no conflict of interest to report.

Figures

Fig. 1
Fig. 1
PD-proteins in clathrin-mediated endocytosis. Stages in clathrin-mediated endocytosis (CME) and the suggested involvement of PD-associated proteins at specific stages of the process. Created with BioRender.com.
Fig. 2
Fig. 2
PD- and PIP-associated proteins in vesicular trafficking. The distribution of PD- and PIP-associated proteins in cellular mechanisms of vesicular membrane trafficking, and the relevant PIPs. Proteins involved in both mechanisms, macroautophagy and CME (α-Syn, LRRK2, SJ1 and endophilin A); mitophagy (PINK1 and DJ1); and endo-lysosomal proteins (ATP13A2, VAC14, VPS35, Rab5 and Rab7). Created with BioRender.com.
See this image and copyright information in PMC

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