The Unfolded Protein Response in Immune Cells as an Emerging Regulator of Neuroinflammation

Dominique Fernández, Antonia Geisse, Jose Ignacio Bernales, Alonso Lira, Fabiola Osorio

Keywords: UPR, neurodegeneration, microglia, inflammation, neuroinflammation, protein misfolding, ER stress, immune system


Immune surveillance is an essential process that safeguards the homeostasis of a healthy brain. Among the increasing diversity of immune cells present in the central nervous system (CNS), microglia have emerged as a prominent leukocyte subset with key roles in the support of brain function and in the control of neuroinflammation. In fact, impaired microglial function is associated with the development of neurodegenerative diseases, including Alzheimer’s disease (AD) and Parkinson’s disease (PD). Interestingly, these pathologies are also typified by protein aggregation and proteostasis dysfunction at the level of the endoplasmic reticulum (ER). These processes trigger activation of the unfolded protein response (UPR), which is a conserved signaling network that maintains the fidelity of the cellular proteome. Remarkably, beyond its role in protein folding, the UPR has also emerged as a key regulator of the development and function of immune cells. However, despite this evidence, the contribution of the UPR to immune cell homeostasis, immune surveillance, and neuro-inflammatory processes remains largely unexplored. In this review, we discuss the potential contribution of the UPR in brain- associated immune cells in the context of neurodegenerative diseases.

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Título de la Revista: Frontiers in Marine Science
Volumen: 13
Número: 682633
Editorial: Elsevier
Fecha de publicación: 2021
Página de inicio: 1
Página final: 9
Idioma: English

doi: 10.3389/fnagi.2021.682633