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

Author(s)

Chiarotto, Gabriela Bortolanca ^[1] ; Nardo, Giovanni ^[2] ; Trolese, Maria Chiara ^[2] ; Franca, Jr., Marcondes Cavalcante ^[3] ; Bendotti, Caterina ^[2] ; Rodrigues de Oliveira, Alexandre Leite ^[1]

Affiliation

^[1] Inst Biol Unicamp, Dept Struct & Funct Biol, BR-13083865 Campinas, SP - Brazil

^[2] IRCCS Inst Pharmacol Res Mario Negri, Dept Neurosci, I-20156 Milan - Italy

^[3] Fac Med Sci Unicamp, Dept Neurol, BR-13083887 Campinas, SP - Brazil

• Document type: Review article
• Source: INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 18, n. 11 NOV 2017.
• Web of Science Citations: 1

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 degenerating motor axons accelerating collateral reinnervation of muscles. (AU)

• FAPESP's process: 14/06892-3 - Use of mesenchymal stem cells in the CNS/PNS interface: repair of proximal lesions
• Grantee: Alexandre Leite Rodrigues de Oliveira
• Support type: Research Projects - Thematic Grants
• FAPESP's process: 13/16168-8 - Administration of riluzole, tempol and mesenchymal stem cells in the treatment of ALS in SOD1 G93A mice
• Grantee: Gabriela Bortolança Chiarotto
• Support type: Scholarships in Brazil - Doctorate
• FAPESP's process: 17/02895-6 - Role of MHC Class I on ALS progression in 129Sv-G93A mice
• Grantee: Gabriela Bortolança Chiarotto
• Support type: Scholarships abroad - Research Internship - Doctorate