The role of lipids in autophagy and its implication in neurodegeneration.

Sandra-Fausia Soukup,Sergio Hernandez-Diaz

doi:10.15698/cst2020.07.225

Abstract

Neurodegenerative diseases are, at present, major socio-economic burdens without effective treatments and their increasing prevalence means that these diseases will be a challenge for future generations. Neurodegenerative diseases may differ in etiology and pathology but are often caused by the accumulation of dysfunctional and aggregation-prone proteins. Autophagy, a conserved cellular mechanism, deals with cellular stress and waste product build-up and has been shown to reduce the accumulation of dysfunctional proteins in animal models of neurodegenerative diseases. Historically, progress in understanding the precise function of lipids has traditionally been far behind other biological molecules (like proteins) but emerging works demonstrate the importance of lipids in the autophagy pathway and how the disturbance of lipid metabolism is connected to neurodegeneration. Here we review how altered autophagy and the disturbance of lipid metabolism, particularly of phosphoinositols and sphingolipids, feature in neurodegenerative diseases and address work from the field that suggests that these potentially offer an opportunity of therapeutic intervention.

Highlights

The prevalence of neurodegenerative disease like Alzheimer’s (AD) and Parkinson’s (PD) diseases will double in the coming years [1,2,3]
In this review we highlighted the function of lipids in various stages of the autophagy pathway, where they can act as recognition motif to attract regulatory autophagy complexes, to regulate the autophagy core machinery as bioactive lipids or even by regulating transcription of ATGs (Figure 6)
Alterations of the lipid metabolism leads to defects in the autophagy pathway, illustrating the tight connection between lipid supply and the formation/progression of the autophagosome

Summary

Introduction

The prevalence of neurodegenerative disease like Alzheimer’s (AD) and Parkinson’s (PD) diseases will double in the coming years [1,2,3]. Emerging evidence shows that autophagy is altered in many neurodegenerative diseases and that defects in the autophagy pathway lead to the accumulation of dysfunctional and aggregation-prone proteins. The presence and local production of the phospholipids like PI3P is critical to define the origin of autophagic membranes, as well as to recruit key protein complexes acting in autophagosome biogenesis, maturation and trafficking.

Results

Conclusion