Microglia in the aging brain: relevance to neurodegeneration - PubMed (original) (raw)
Microglia in the aging brain: relevance to neurodegeneration
Xiao-Guang Luo et al. Mol Neurodegener. 2010.
Abstract
Microglia cells are the brain counterpart of macrophages and function as the first defense in the brain. Although they are neuroprotective in the young brain, microglia cells may be primed to react abnormally to stimuli in the aged brain and to become neurotoxic and destructive during neurodegeneration. Aging-induced immune senescence occurs in the brain as age-associated microglia senescence, which renders microglia to function abnormally and may eventually promote neurodegeneration. Microglia senescence is manifested by both morphological changes and alterations in immunophenotypic expression and inflammatory profile. These changes are likely caused by microinvironmental factors, but intrinsic factors cannot yet be completely excluded. Microglia senescence appears to underlie the switching of microglia from neuroprotective in the young brain to neurotoxic in the aged brain. The hypothesis of microglia senescence during aging offers a novel perspective on their roles in aging-related neurodegeneration. In Parkinson's disease and Alzheimer's disease, over-activation of microglia may play an active role in the pathogenesis because microglia senescence primes them to be neurotoxic during the development of the diseases.
Figures
Figure 1
Age-primed microglia hypothesis of Parkinson's disease. Microglia functions differentially in the substantia nigra of the young (left) and aged (right) brain. Left: When facing pathogenic stimuli (large black dots), the healthy microglia in the young brain respond by releasing neurotrophic factors (small yellow dots) to support the endangered dopaminergic neurons and limit neuronal damages. Right: In the aged brain the microglia are primed with aging and function abnormally. When exposed to pathogenic stimuli, they are overactivated and release excessive oxidative stress and inflammatory factors (small black dots), which damage the vulnerable dopaminergic neurons and eventually lead to neurodegeneration.
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