Molecular Neurobiology

, Volume 53, Issue 7, pp 4638–4658 | Cite as

The Deleterious Effects of Oxidative and Nitrosative Stress on Palmitoylation, Membrane Lipid Rafts and Lipid-Based Cellular Signalling: New Drug Targets in Neuroimmune Disorders

  • Gerwyn Morris
  • Ken Walder
  • Basant K. Puri
  • Michael Berk
  • Michael Maes


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.


Oxidative and nitrosative stress Inflammation Metabolism Depression Cytokines Chronic fatigue 



The authors would like to express their thanks to Victoria Storey for her invaluable secretarial services. No specific funding was obtained for this specific review.

Competing Interests

The authors declare that they have no competing interests.

Authors’ Contributions

GM and MM participated in the design of this review, while KW, BKP and MB helped to draft the paper. All authors read and approved the final version of the manuscript.


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Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Gerwyn Morris
    • 1
  • Ken Walder
    • 2
  • Basant K. Puri
    • 3
  • Michael Berk
    • 4
    • 5
    • 6
    • 7
  • Michael Maes
    • 7
    • 8
    • 9
  1. 1.Tir Na NogLlanelliUK
  2. 2.Metabolic Research UnitDeakin UniversityGeelongAustralia
  3. 3.Department of Medicine, Hammersmith HospitalImperial College LondonLondonUK
  4. 4.Orygen, The National Centre of Excellence in Youth Mental Health and the Centre of Youth Mental HealthParkvilleAustralia
  5. 5.The Florey Institute for Neuroscience and Mental HealthUniversity of MelbourneParkvilleAustralia
  6. 6.Department of Psychiatry, Royal Melbourne HospitalUniversity of MelbourneParkvilleAustralia
  7. 7.IMPACT Strategic Research Center, School of MedicineDeakin UniversityGeelongAustralia
  8. 8.Department of Psychiatry, Faculty of MedicineChulalongkorn UniversityBangkokThailand
  9. 9.Health Sciences Graduate Program, Health Sciences CenterState University of LondrinaLondrinaBrazil

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