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REVIEW article

Front. Mol. Biosci.
Sec. Cellular Biochemistry
Volume 11 - 2024 | doi: 10.3389/fmolb.2024.1455817
This article is part of the Research Topic Cellular Contributors and Consequences of Protein Misfolding and Aggregation View all 3 articles

Lipids and -Synuclein: Adding further variables to the equation

Provisionally accepted
Jana Schepers Jana Schepers *Timo Löser Timo Löser Christian Behl Christian Behl *
  • Institute of Pathobiochemistry, University Medical Centre, Johannes Gutenberg University Mainz, Mainz, Germany

The final, formatted version of the article will be published soon.

    Aggregation of alpha-Synuclein (Syn) 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 Syn to negatively charged phospholipids have been well described and are connected to putative physiological functions of Syn. Consequently, Syn-related neurodegeneration has been increasingly connected to changes in lipid metabolism and membrane lipid composition. Indeed, Syn 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, Syn 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 Syn 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 Syn and discuss open questions that need to be answered to further our knowledge of Syn related neurodegeneration.

    Keywords: alpha-Synuclein, Parkinson's disease, DLB, MSA, Membrane Lipids, Lipid Metabolism

    Received: 27 Jun 2024; Accepted: 26 Jul 2024.

    Copyright: © 2024 Schepers, Löser and Behl. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Jana Schepers, Institute of Pathobiochemistry, University Medical Centre, Johannes Gutenberg University Mainz, Mainz, Germany
    Christian Behl, Institute of Pathobiochemistry, University Medical Centre, Johannes Gutenberg University Mainz, Mainz, Germany

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