Microglia and Peripheral Immune Cells in Aging and Neurodegenerative Diseases

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About this Research Topic

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Background

The immune system plays an essential role in homeostasis and pathological processes of the central nervous system (CNS), including the brain and retina. Conceptualizing neurodegenerative disease as a “neuron-centric” disorder has been shifted into a more “immune-centric “view in recent years. Dysregulated immune responses as a cardinal feature of neurodegenerative diseases was previously thought to be restricted to the immune environment in the CNS, but evidence highlighting the pivotal contributions of the peripheral immune system has been increasingly acknowledged. As the principal resident immune cells of CNS, microglial dysregulation is highly implicated in the pathogenesis of different neurodegenerative diseases, either via promoting neuroinflammation or indirectly in response to cues from the peripheral immune system. Phenotypic and functional alterations of innate and adaptive immune components from the periphery also contribute to many aspects of neurodegenerative pathology.

Aging is a major risk factor for neurodegenerative diseases, which can lead to functional decline of both the CNS and peripheral immune system. Senescent alterations of microglia have been linked to compromised phagocytic capacity and neuroinflammation. Moreover, senescence of peripheral immune system cells also curtails the ability to mount protective immune responses to cope with neurodegenerative pathology. In this regard, studies of the physiological changes during aging will facilitate our understanding of pathological alterations of age-related neurodegenerative diseases.



Despite a close correlation of dysregulated immune responses with CNS aging and neurodegenerative pathology, the heterogeneous nature of both CNS resident microglia and peripheral immune cells has impeded characterization of their role and crosstalk in regulating these processes. Many important questions remain to be addressed: Whether the peripheral and central immune compartments dynamically change over time during aging and neurodegenerative disorders? How these changes contribute to the pathology of neurodegenerative diseases? Can we target microglia and/or peripheral immune cells to maintain their healthy function during aging, thereby delaying or inhibiting the onset or progression of neurodegenerative diseases? A comprehensive understanding of how peripheral immune cells act in concert with the CNS resident microglia to regulate aging processes and neurodegenerative diseases will surely provide novel insights and guidance for the development of next-generation immunotherapies for various age-related neurodegenerative diseases.



For this Research Topic, we welcome submissions of original research and reviews that focus on the emerging role of microglia, peripheral immune cells and their crosstalk in aging and neurodegenerative diseases in the brain and retina, including in Alzheimer’s disease, multiple sclerosis, age-related macular degeneration (AMD) and diabetic retinopathy (DR). The topics include but are not limited to:

• Descriptions of phenotypic and functional alterations of microglia and peripheral immune cells in the aging brain and retina

• The role and underlying mechanisms of microglial and peripheral innate and adaptive immune cells in neurodegenerative diseases

• Crosstalk between microglia and the peripheral immune system in neurodegenerative diseases

• Therapeutic strategies and clinical interventions which modulate microglia and/or peripheral immune components in neuroinflammatory and neurodegenerative diseases

Keywords: microglia, periphery immune cells, brain, retina, aging, neurodegenerative disease, neuroinflammation

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