Laboratory of Cell Biophysics, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw 02-093, Poland.
Genetics and Aging Research Unit, Department of Neurology, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02115.
J Neurosci. 2024 Oct 2;44(40):e1225242024. doi: 10.1523/JNEUROSCI.1225-24.2024.
Palmitoylation, a lipid-based posttranslational protein modification, plays a crucial role in regulating various aspects of neuronal function through altering protein membrane-targeting, stabilities, and protein-protein interaction profiles. Disruption of palmitoylation has recently garnered attention as disease mechanism in neurodegeneration. Many proteins implicated in neurodegenerative diseases and associated neuronal dysfunction, including but not limited to amyloid precursor protein, β-secretase (BACE1), postsynaptic density protein 95, Fyn, synaptotagmin-11, mutant huntingtin, and mutant superoxide dismutase 1, undergo palmitoylation, and recent evidence suggests that altered palmitoylation contributes to the pathological characteristics of these proteins and associated disruption of cellular processes. In addition, dysfunction of enzymes that catalyze palmitoylation and depalmitoylation has been connected to the development of neurological disorders. This review highlights some of the latest advances in our understanding of palmitoylation regulation in neurodegenerative diseases and explores potential therapeutic implications.
棕榈酰化作用，一种基于脂质的翻译后蛋白质修饰，通过改变蛋白质的膜靶向、稳定性和蛋白质-蛋白质相互作用谱，在调节神经元功能的各个方面中起着至关重要的作用。棕榈酰化作用的破坏最近作为神经退行性疾病的发病机制引起了关注。许多与神经退行性疾病和相关神经元功能障碍相关的蛋白质，包括但不限于淀粉样前体蛋白、β-分泌酶 (BACE1)、突触后密度蛋白 95、Fyn、突触结合蛋白-11、突变型亨廷顿蛋白和突变型超氧化物歧化酶 1，都经历棕榈酰化作用，最近的证据表明，改变棕榈酰化作用导致这些蛋白质的病理特征以及相关细胞过程的破坏。此外，催化棕榈酰化和去棕榈酰化的酶的功能障碍与神经障碍的发展有关。这篇综述强调了我们在理解神经退行性疾病中棕榈酰化调节方面的一些最新进展，并探讨了潜在的治疗意义。
