Microglial Polarization in the Pathogenesis and Therapeutics of Neurodegenerative Diseases

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About this Research Topic

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Background

This Research Topic is the first part of the article collection series: Microglial Polarization in the Pathogenesis and Therapeutics of Neurodegenerative Diseases, Volume II.

Neurodegenerative diseases are a clinically heterogeneous group of disorders characterized by the progressive degeneration of the neurons and their functions in the central nervous system (CNS) or peripheral nervous system (PNS), including Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), Amyotrophic lateral sclerosis (ALS), Spinal muscular atrophy (SMA), Multiple Sclerosis (MS), and so forth. One of the most prominent features shared by various neurodegenerative diseases is microglia-mediated neuroinflammation. Microglial activation is the principal component of neuroinflammation, which is now considered to execute both detrimental and beneficial effects on the neurons. Depending on the milieu in which microglia become activated or the insults by which they are stimulated, the polarization of microglia shows to be heterogeneous with diverse functional phenotypes that range from pro-inflammatory M1 phenotypes to immunosuppressive M2 phenotypes. The M1/M2 paradigm is actually a simplified model to depict the two polars of the inflammatory responses of microglia. M1 microglia originally act in the first line to defense tissue and revoke acute inflammation to protect against invading pathogens. However, they also induce extensive neurotoxicity, due to the release of various pro-inflammatory factors and neurotoxic mediators. Generally after the onset of M1 polarization, an anti-inflammatory and repair process is rapidly initiated in attempt to bring back tissue homeostasis. M2 microglia are the major effectors that can dampen pro-inflammatory immune responses, stimulate tissue repair, remove toxic aggregated proteins and cell debris, and enhance the secretion of neurotrophic factors to prevent neural injury. However, neurodegenerative diseases commonly implicate the persistent M1 pro-inflammatory responses, and failure in the resolution of neuroinflammation and tissue repair. Interestingly, aging as one of the most important risk factors for the pathogenesis of neurodegenerative diseases, may also give rise to altered M1/M2 inflammatory profiles. Thus, stage-specific switching of the M1/M2 microglial polarization within appropriate time windows might produce therapeutic benefits to neurodegenerative diseases.

In this research topic, researchers and clinicians will explore and discuss the potential mechanisms of M1/M2 microglial polarization that are critically associated with multiple neurodegenerative diseases. The possible link between aging and the immune-pathogenesis will be deciphered. Finally, the immunotherapy by switching M1/M2 balance and other novel therapeutic approaches will also be covered.

Keywords: Neurodegenerative diseases, Neuroinflammation, Microglial Polarization, M1 Microglia, M2 Microglia, M1/M2 Switch, Aging

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