The Emerging Role of the Major Histocompatibility Complex Class I in Amyotrophic Lateral Sclerosis

International Journal of Molecular Sciences
Gabriela Bortolança ChiarottoAlexandre Leite Rodrigues de Oliveira

Abstract

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease affecting upper and lower motoneurons (MNs). The etiology of the disease is still unknown for most patients with sporadic ALS, while in 5-10% of the familial cases, several gene mutations have been linked to the disease. Mutations in the gene encoding Cu, Zn superoxide dismutase (SOD1), reproducing in animal models a pathological scenario similar to that found in ALS patients, have allowed for the identification of mechanisms relevant to the ALS pathogenesis. Among them, neuroinflammation mediated by glial cells and systemic immune activation play a key role in the progression of the disease, through mechanisms that can be either neuroprotective or neurodetrimental depending on the type of cells and the MN compartment involved. In this review, we will examine and discuss the involvement of major histocompatibility complex class I (MHCI) in ALS concerning its function in the adaptive immunity and its role in modulating the neural plasticity in the central and peripheral nervous system. The evidence indicates that the overexpression of MHCI into MNs protect them from astrocytes' toxicity in the central nervous system (CNS) and promote the removal of degenera...Continue Reading

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Citations

Aug 11, 2018·Molecular Neurodegeneration·Giovanni NardoCaterina Bendotti
Dec 18, 2018·Clinical & Experimental Neuroimmunology·Emiliano TriasKoji Yamanaka
May 7, 2020·Frontiers in Neurology·Pamela A McCombeRobert D Henderson
Sep 13, 2021·Clinical and Experimental Immunology·Sandra AmorFabiola Puentes

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Methods Mentioned

BETA
transgenic
biopsies

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