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Biochemistry (Moscow)

, Volume 83, Issue 9, pp 1104–1116 | Cite as

Immunogenetic Factors of Neurodegenerative Diseases: The Role of HLA Class II

  • M. P. AliseychikEmail author
  • T. V. Andreeva
  • E. I. RogaevEmail author
Review
  • 68 Downloads

Abstract

An increase in the life expectancy during the last decades in most world countries has resulted in the growing number of people suffering from neurodegenerative disorders, including Alzheimer’s disease, Parkinson’s disease, fron-totemporal dementia, and others. Familial forms of neurodegenerative diseases account for 5–10% of all cases and are caused by mutations in specific genes often resulting in pathological protein deposition. The risk factors for neurodegeneration include trauma, lifestyle, and allelic variants of disease-associated genes with incomplete penetrance. Many of these gene variants are located in immunity-related loci, particularly in the human leukocyte antigen locus (HLA class II) coding for proteins of the major histocompatibility complex class II (MHCII). HLA class II plays a key role in the antigen presentation and is expressed in microglial cells. Microglia is a component of innate immunity. On the one hand, microglial cells phagocytize pathological protein deposits; on the other hand, they produce proinflammatory factors accelerating neuronal death. The involvement of adaptive immunity mechanisms (antigen presentation, T cell response, antibody production) in the development of neurodegenerative diseases remains unclear and requires further research, including more detailed studies of the role of identified HLA class II genetic variants.

Keywords

human leukocyte antigen major histocompatibility complex class II neurodegeneration Alzheimer’s disease Parkinson’s disease genome-wide association study 

Abbreviations

ALS

amyotrophic lateral sclerosis

ApoE

apolipoprotein E

CNS

central nervous system

GWAS

genome-wide association study

HLA

human leucocyte antigen

IL

interleukin

IFNγ

interferon γ

MHC

major histocompatibility complex

MHCI(II)

major histocompatibility complex class I(II)

PD

Parkinson’s disease

TNF

tumor necrosis factor

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Copyright information

© Pleiades Publishing, Ltd. 2018

Authors and Affiliations

  1. 1.Vavilov Institute of General GeneticsRussian Academy of Sciences, Department of Genomics and Human GeneticsMoscowRussia
  2. 2.Center for Genetics and Genetic Technologies, Department of BiologyLomonosov Moscow State UniversityMoscowRussia
  3. 3.Department of PsychiatryUniversity of Massachusetts Medical SchoolWorcesterUSA

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