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.
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http://dx.doi.org/10.1186/s11658-024-00625-2 | DOI Listing |
Nat Commun
January 2025
Shenzhen Key Laboratory of Gene Regulation and Systems Biology, and Brain Research Center, Department of Neuroscience, School of Life Sciences, Southern University of Science and Technology, Shenzhen, China.
Optogenetics is a valuable tool for studying the mechanisms of neurological diseases and is now being developed for therapeutic applications. In rodents and macaques, improved channelrhodopsins have been applied to achieve transcranial optogenetic stimulation. While transcranial photoexcitation of neurons has been achieved, noninvasive optogenetic inhibition for treating hyperexcitability-induced neurological disorders has remained elusive.
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January 2025
Department of Occupational and Environmental Health, School of Public Health, Jinzhou Medical University, Jinzhou, Liaoning, PR China. Electronic address:
Flame retardant polybrominated diphenyl ethers (PBDEs) accumulate in human bodies through food and dust ingestion, and cause neurobehavioral deficits with obscure mechanism. We aimed to investigate NMDAR-CaMKⅡγ-mediated synapse-to-nuclear communication involved in BDE-209-induced cognitive impairment, and alleviation from exogenous melatonin. Decreased NMDAR subunits GluN2A and 2B, autophosphorylation of CaMKⅡα, and postsynaptic GluA1 trafficking were observed in the hippocampus of juvenile rats after maternal BDE-209 exposure.
View Article and Find Full Text PDFMatrix Biol
January 2025
German Center for Neurodegenerative Diseases (DZNE), Helmholtz Association of German Research Centers, Magdeburg, Germany; Center for Behavioral Brain Sciences (CBBS), Magdeburg, Germany; Medical Faculty, Otto-von-Guericke University, Magdeburg, Germany. Electronic address:
The neural extracellular matrix (ECM) accumulates in the form of perineuronal nets (PNNs), particularly around fast-spiking GABAergic interneurons in the cortex and hippocampus, but also around synapses and in association with the axon initial segments (AIS) and nodes of Ranvier. Increasing evidence highlights the role of Neurocan (Ncan), a brain-specific component of ECM, in the pathophysiology of neuropsychiatric disorders like bipolar disorder and schizophrenia. Ncan localizes at PNNs, perisynaptically, and at the nodes of Ranvier and the AIS, highlighting its potential role in regulating axonal excitability.
View Article and Find Full Text PDFBiomed Pharmacother
January 2025
Department of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, Italy. Electronic address:
Cannabis derivatives are among the most widely used psychoactive substances in the world, which leads to growing medical concerns regarding its chronic use and abuse especially among adolescents. Exposure to THC during formative years produces long-term behavioral alterations that share similarities with symptoms of psychiatric and neurodevelopmental disorders. In this study, we have analyzed the functional and molecular mechanisms that might underlie these alterations.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Neurophysiology & Behaviour Lab, University of Castilla-La Mancha, Ciudad Real, Spain.
Background: A key neuropathological feature in the early stages of Alzheimer's disease (AD) involves hippocampal dysfunction arising from the accumulation of amyloid-β (Aβ). Previously, our laboratory identified a shift in the synaptic plasticity long term potentiation (LTP)/long term depression (LTD) induction threshold, leading to memory deficits in a non-transgenic murine model of early AD generated by intracerebroventricular (icv.) injections Aβ oligomers (oAβ), one of the most predominant pathogenetic factors in initial stages of the disease.
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