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Chronically active: activation of microglial proteolysis in ageing and neurodegeneration
journal contributionposted on 05.03.2015, 15:06 by Alexandra StolzingAlexandra Stolzing, Sebastian Sethe, Tilman Grune
One of the microglial cell functions is the removal of modified extracellular proteins in the brain. The connection between protein oxidation, proteolysis, and microglial activation is the topic of this review. The effect of various activation agents on microglial cells with regard to changes in substrate uptake, proteolytic capacity and degradation efficiency of different types of oxidized protein materials is reviewed. It is shown that different activation stimuli initiate substrate-specific modulation for uptake and proteolysis, influencing an array of factors including receptor expression, lysosomal pH, and proteasome subunit composition. Age-related alterations in activation and proteolytic capacity in microglial cells are also discussed. In ageing, proteolytic effectiveness is diminished, while microglial cells are chronically activated and lose the oxidative burst ability, possibly supporting a 'vicious circle' of macrophage-induced neurodegeneration. © W. S. Maney & Son Ltd.
TG was supported by the DFG, GRK1033 and SFB575.
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