Classical MHC Class I Molecules as Modifiers of Brain Homeostasis and Neuroregeneration: Unraveling the Riddle?

Abstract

As mankind breaks the boundaries of potential years to live, the process of aging imposes various cellular challenges, from less capacity of cell repair and damage to impaired protein formation, causing chronic low-level inflammation on tissues including the brain. Persistent chronic neuroinflammation can harm neurons, contributing to the development of neurodegeneration, a pathological process that affects cognitive function and is often reflected by dementia. This opinion article tries to recapitulate the influence that major histocompatibility class I (MHC-I) molecules have on brain homeostasis and how abnormalities in their expression can lead to cognitive deterioration. Studies carried out during recent years not only demonstrated that neurons and other central nervous system (CNS) cells express MHC-I molecules, but also that these molecules play essential roles in the establishment, function, and modeling of synapses in the CNS during the embryonic period, at birth and during adulthood, namely during inflammatory conditions. The accumulated body of evidence suggests that MHC-I molecules and the signaling pathways they regulate could provide clues on some of the molecular and cellular mechanisms regulating brain homeostasis and neuroregeneration in health and disease, thus becoming potential biomarkers of cognitive decline and targets for innovative immunotherapies.

Keywords

Aging / Alzheimer’s disease (AD) / Central nervous system (CNS) / Cognitive impairment / Cytoplasmic MHC-I tail / Dementia / MHC-I conformers / Parkinson’s disease (PD)

Acknowledgments

This work is part of the M.Sc. thesis of Ricardo Carvalho.

Author Contributions

F.A.A. and R.A.S.C. wrote the manuscript; F.A.A. elaborated the figures; E.M.C. reviewed and edited the manuscript and figures.

Ethics Statement

Not applicable.

Informed Consent Statement

Not applicable.

Funding

The writing of this opinion article received no external funding.

Declaration of Competing Interest

The authors declare that they have no known competing financial interests or personal relationships that could haveappeared to influence the work reported in this paper.

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