title: The Deleterious Effects of Oxidative and Nitrosative Stress on Palmitoylation, Membrane Lipid Rafts and Lipid-Based Cellular Signalling: New Drug Targets in Neuroimmune Disorders.
abstract: Oxidative and nitrosative stress (O&NS) is causatively implicated in the pathogenesis of Alzheimer's and Parkinson's disease, multiple sclerosis, chronic fatigue syndrome, schizophrenia and depression. Many of the consequences stemming from O&NS, including damage to proteins, lipids and DNA, are well known, whereas the effects of O&NS on lipoprotein-based cellular signalling involving palmitoylation and plasma membrane lipid rafts are less well documented. The aim of this narrative review is to discuss the mechanisms involved in lipid-based signalling, including palmitoylation, membrane/lipid raft (MLR) and n-3 polyunsaturated fatty acid (PUFA) functions, the effects of O&NS processes on these processes and their role in the abovementioned diseases. S-palmitoylation is a post-translational modification, which regulates protein trafficking and association with the plasma membrane, protein subcellular location and functions. Palmitoylation and MRLs play a key role in neuronal functions, including glutamatergic neurotransmission, and immune-inflammatory responses. Palmitoylation, MLRs and n-3 PUFAs are vulnerable to the corruptive effects of O&NS. Chronic O&NS inhibits palmitoylation and causes profound changes in lipid membrane composition, e.g. n-3 PUFA depletion, increased membrane permeability and reduced fluidity, which together lead to disorders in intracellular signal transduction, receptor dysfunction and increased neurotoxicity. Disruption of lipid-based signalling is a source of the neuroimmune disorders involved in the pathophysiology of the abovementioned diseases. n-3 PUFA supplementation is a rational therapeutic approach targeting disruptions in lipid-based signalling.
authors: Tir Na Nog, Bryn Road seaside 87, Llanelli, SA152LW, Wales, UK.
authors: Gerwyn
authors: G
authors: Morris
authors: Metabolic Research Unit, Deakin University, Geelong, Australia.
authors: Ken
authors: K
authors: Walder
authors: Department of Medicine, Hammersmith Hospital, Imperial College London, London, W12 0HS, UK.
authors: Basant K
authors: BK
authors: Puri
authors: Orygen, The National Centre of Excellence in Youth Mental Health and the Centre of Youth Mental Health, Poplar Road 35, Parkville, 3052, Australia.|The Florey Institute for Neuroscience and Mental Health, University of Melbourne, Kenneth Myer Building, Royal Parade 30, Parkville, 3052, Australia.|Department of Psychiatry, Royal Melbourne Hospital, University of Melbourne, Level 1 North, Main Block, Parkville, 3052, Australia.|IMPACT Strategic Research Center, School of Medicine, Deakin University, P.O. Box 291, Geelong, 3220, Australia.
authors: Michael
authors: M
authors: Berk
authors: IMPACT Strategic Research Center, School of Medicine, Deakin University, P.O. Box 291, Geelong, 3220, Australia. dr.michaelmaes@hotmail.com.|Department of Psychiatry, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. dr.michaelmaes@hotmail.com.|Health Sciences Graduate Program, Health Sciences Center, State University of Londrina, Londrina, Brazil. dr.michaelmaes@hotmail.com.
authors: Michael
authors: M
authors: Maes
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D016503:Drug Delivery Systems / Q000639:trends; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage; D006801:Humans; D054878:Lipoylation / Q000187:drug effects / Q000502:physiology*; D021962:Membrane Microdomains / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D009422:Nervous System Diseases / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism*; D015213:Neuroimmunomodulation / Q000187:drug effects / Q000502:physiology; D000073039:Nitrosative Stress / Q000187:drug effects / Q000502:physiology*; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
chemical_list: D015525:Fatty Acids, Omega-3
keywords: Chronic fatigue; Cytokines; Depression; Inflammation; Metabolism; Oxidative and nitrosative stress