Lost in traffic: consequences of altered palmitoylation in neurodegeneration.

Autor:	Ramzan F; NeurdyPhagy Lab, Department of Biology, Faculty of Science, University of Waterloo, Waterloo, ON, Canada., Abrar F; NeurdyPhagy Lab, Department of Biology, Faculty of Science, University of Waterloo, Waterloo, ON, Canada., Mishra GG; NeurdyPhagy Lab, Department of Biology, Faculty of Science, University of Waterloo, Waterloo, ON, Canada., Liao LMQ; NeurdyPhagy Lab, Department of Biology, Faculty of Science, University of Waterloo, Waterloo, ON, Canada., Martin DDO; NeurdyPhagy Lab, Department of Biology, Faculty of Science, University of Waterloo, Waterloo, ON, Canada.
Jazyk:	angličtina
Zdroj:	Frontiers in physiology [Front Physiol] 2023 May 30; Vol. 14, pp. 1166125. Date of Electronic Publication: 2023 May 30 (Print Publication: 2023).
DOI:	10.3389/fphys.2023.1166125
Abstrakt:	One of the first molecular events in neurodegenerative diseases, regardless of etiology, is protein mislocalization. Protein mislocalization in neurons is often linked to proteostasis deficiencies leading to the build-up of misfolded proteins and/or organelles that contributes to cellular toxicity and cell death. By understanding how proteins mislocalize in neurons, we can develop novel therapeutics that target the earliest stages of neurodegeneration. A critical mechanism regulating protein localization and proteostasis in neurons is the protein-lipid modification S-acylation, the reversible addition of fatty acids to cysteine residues. S-acylation is more commonly referred to as S-palmitoylation or simply palmitoylation, which is the addition of the 16-carbon fatty acid palmitate to proteins. Like phosphorylation, palmitoylation is highly dynamic and tightly regulated by writers (i.e., palmitoyl acyltransferases) and erasers (i.e., depalmitoylating enzymes). The hydrophobic fatty acid anchors proteins to membranes; thus, the reversibility allows proteins to be re-directed to and from membranes based on local signaling factors. This is particularly important in the nervous system, where axons (output projections) can be meters long. Any disturbance in protein trafficking can have dire consequences. Indeed, many proteins involved in neurodegenerative diseases are palmitoylated, and many more have been identified in palmitoyl-proteomic studies. It follows that palmitoyl acyl transferase enzymes have also been implicated in numerous diseases. In addition, palmitoylation can work in concert with cellular mechanisms, like autophagy, to affect cell health and protein modifications, such as acetylation, nitrosylation, and ubiquitination, to affect protein function and turnover. Limited studies have further revealed a sexually dimorphic pattern of protein palmitoylation. Therefore, palmitoylation can have wide-reaching consequences in neurodegenerative diseases. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Ramzan, Abrar, Mishra, Liao and Martin.)
Databáze:	MEDLINE
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