1 Nature medicine 2006 Vol: 12(8):885-887. DOI: 10.1038/nm0806-885

ALS: life and death in a bad neighborhood.

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Figure 1: Microglia respond to several types of immunological alarm signals.Endogenous factors include cytokines, material from apoptotic cells and aggregated proteins such as prions. Exogenous factors include viral envelope glycoproteins. In response, microglia can undergo several different levels of activation, finally resulting in a fully functioning phagocytic cell. Activated microglia can be friends or foes to neighboring neurons. As friends, they can clear toxic material (apoptotic neurons, protein aggregates), secrete neurotrophic factors such as BDNF and protective factors such as glutathione and increase clearance of excitotoxic glutamate by astrocytes. Microglia can also secrete potentially neurotoxic molecules such as proinflammatory cytokines (TNF-α, IL-1β), glutamate, free radical species and nitric oxide. Findings by Boillee et al. suggest that microglia have a central role in neuronal damage in ALS; but because these cells also have a friendly side, it's not yet clear how to manipulate them to minimize their damaging effects.Kim Caesar
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