Lipids and α-Synuclein : adding further variables to the equation
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Abstract
Aggregation of alpha-Synuclein (αSyn) has been connected to several
neurodegenerative diseases, such as Parkinson’s disease (PD), dementia with
Lewy Bodies (DLB), and multiple system atrophy (MSA), that are collected
under the umbrella term synucleinopathies. The membrane binding abilities of
αSyn to negatively charged phospholipids have been well described and are
connected to putative physiological functions of αSyn. Consequently, αSyn related neurodegeneration has been increasingly connected to changes in lipid
metabolism and membrane lipid composition. Indeed, αSyn aggregation has
been shown to be triggered by the presence of membranes in vitro, and some
genetic risk factors for PD and DLB are associated with genes coding for proteins
directly involved in lipid metabolism. At the same time, αSyn aggregation itself
can cause alterations of cellular lipid composition and brain samples of patients
also show altered lipid compositions. Thus, it is likely that there is a reciprocal
influence between cellular lipid composition and αSyn aggregation, which can
be further affected by environmental or genetic factors and ageing. Little is
known about lipid changes during physiological ageing and regional differences
of the lipid composition of the aged brain. In this review, we aim to summarise
our current understanding of lipid changes in connection to αSyn and discuss
open questions that need to be answered to further our knowledge of αSyn
related neurodegeneration.
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Frontiers in molecular biosciences, 11, Frontiers, Lausanne, 2024, https://doi.org/10.3389/fmolb.2024.1455817