The role of lipids in autophagy and its implication in neurodegeneration

Abstract

Neurodegenerative diseases are, at present, major socioeconomic 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.

Regulation of Membrane Phospholipid Homeostasis in Neurodegenerative Diseases

“…This reaction occurs via exchanges of inositol and CMP on CDP-GAD, thus producing PI [61]. Remodelling of PI post de novo synthesis is an additional step for the PI species to achieve a desired acyl group composition [62].…”

Zinc provides neuroprotection by regulating NLRP3 inflammasome through autophagy and ubiquitination in a spinal contusion injury model

“…Subsequently, the outer membrane fuses with the lysosome to form a functionally degrading autophagic vesicle which is commonly known as autophagy lysosome. 17 The enzyme in the lysosome degrades the contents of the autophagic vesicle and the inner membrane to perform autophagy effect. Autophagy participates in many physiological activities in organisms, including the inhibition of inflammatory chemokine release.…”

Accumulation of Cerebrospinal Fluid Glycerophospholipids and Sphingolipids in Cognitively Healthy Participants With Alzheimer’s Biomarkers Precedes Lipolysis in the Dementia Stage

“…Of eight lipid classes ( Fahy et al, 2009 ), glycerophospholipids (GPs) and sphingolipids (SPs) constitute diverse molecules whose perturbation may be associated with neuronal injury, neuroinflammation ( Russo et al, 2018 ; Leishman et al, 2019 ), and neurodegeneration ( Raszewski et al, 2016 ; Aufschnaiter et al, 2017 ; Dorninger et al, 2020 ; Hernandez-Diaz and Soukup, 2020 ), all features associated with AD pathology. Some brain lipid components have been measured in AD ( Patel and Forman, 2004 ; Lim et al, 2014 ; Garner, 2010 ; Chew et al, 2020 ; Kao et al, 2020 ).…”