Palmitoylation of synaptic proteins: roles in functional regulation and pathogenesis of neurodegenerative diseases

• Published in: Cellular & molecular biology letters Vol. 29; no. 1; pp. 108 - 18
• Main Authors: Peng, Jiaying, Liang, Danchan, Zhang, Zhonghao
• Format: Journal Article
• Language: English
• Published: England BioMed Central 10.08.2024; BMC
• Subjects: Acyltransferases - metabolism; Alzheimer's disease; Animals; Brain research; Cell fusion; Cytoplasm; DHHC; Disease; Endoplasmic reticulum; Enzymes; Exocytosis; Gene expression; Humans; Huntington's disease; Huntingtons disease; Lipoylation; Localization; Membranes; Movement disorders; Nerve Tissue Proteins - genetics; Nerve Tissue Proteins - metabolism; Neurodegenerative diseases; Neurodegenerative Diseases - metabolism; Neurons; Neurotransmission; Palmitoyl acyltransferases; Palmitoylation; Parkinson's disease; Pathophysiology; Physiology; Plasma; Protein transport; Proteins; Reviews; Synapses - metabolism; Synaptic proteins; Synaptic Transmission; Synaptogenesis; Neurodegenerative diseases; Palmitoyl acyltransferases; Palmitoylation; Synaptic proteins; DHHC
• ISSN: 1689-1392; 1425-8153; 1689-1392
• DOI: 10.1186/s11658-024-00625-2

Palmitoylation is a type of lipid modification that plays an important role in various aspects of neuronal function. Over the past few decades, several studies have shown that the palmitoylation of synaptic proteins is involved in neurotransmission and synaptic functions. Palmitoyl acyltransferases (PATs), which belong to the DHHC family, are major players in the regulation of palmitoylation. Dysregulated palmitoylation of synaptic proteins and mutated/dysregulated DHHC proteins are associated with several neurodegenerative diseases, such as Alzheimer's disease (AD), Huntington's disease (HD), and Parkinson's disease (PD). In this review, we summarize the recent discoveries on the subcellular distribution of DHHC proteins and analyze their expression patterns in different brain cells. In particular, this review discusses how palmitoylation of synaptic proteins regulates synaptic vesicle exocytotic fusion and the localization, clustering, and transport of several postsynaptic receptors, as well as the role of palmitoylation of other proteins in regulating synaptic proteins. Additionally, some of the specific known associations of these factors with neurodegenerative disorders are explored, with a few suggestions for the development of therapeutic strategies. Finally, this review provides possible directions for future research to reveal detailed and specific mechanisms underlying the roles of synaptic protein palmitoylation.