Abstract
Neuronal expression of major histocompatibility complex I (MHC-I) has been implicated in developmental synaptic plasticity and axonal regeneration in the central nervous system (CNS), but recent findings demonstrate that constitutive neuronal MHC-I can also be involved in neurodegenerative diseases by playing a neuroinflammtory role. Recent reports demonstrate its expression in vitro and in human postmortem samples and support a role in neurodegeneration involving proinflammatory cytokines, activated microglia and increased cytosolic oxidative stress. Major histocompatibility complex I may be important for both normal development and pathogenesis of some CNS diseases including Parkinson’s.
Highlights
The major histocompatibility complex (MHC) gene family encodes molecules on the surface of cells that enable the immune system to recognize presented self- and foreign-derived peptides (Chemali et al, 2011)
Cultured primary catecholamine murine neurons normally do not express major histocompatibility complex I (MHC-I), but do so upon exposure to IFN-γ, activated microglia or exposure to high levels of L-dihydroxyphenylalanine (L-DOPA), and are far more susceptible to MHC-I induction than other neuronal populations tested, including cortical, striatal and thalamic neurons (Cebrián et al, 2014). These findings suggest that neuronal MHC-I expression and antigen display in catecholamine neurons may be triggered by microglial activation or high cytosolic DA, which in the presence of the appropriate antigen and cytotoxic T lymphocytes (CTLs) could play a role in neuronal death during diseases in which central nervous system (CNS) inflammation is robust
The preference for MHC-I expression by catecholamine neurons was replicated in cultured substantia nigra (SN) DA murine neurons in which MHC-I was induced by IFN-γ and microglia activated by NM or α-syn, substances found extracellularly in postmortem Parkinson’s disease (PD) brain, or by chronic exposure to the DA precursor, L-DOPA, which may be related to intracellular oxidative stress due to high cytosolic levels of its metabolite, DA
Summary
The major histocompatibility complex (MHC) gene family encodes molecules on the surface of cells that enable the immune system to recognize presented self- and foreign-derived peptides (Chemali et al, 2011). MHC-I expression was initially reported in microglia and endothelial cells of the hippocampus in control individuals and Alzheimer’s disease patients (Tooyama et al, 1990), but not in neurons.
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