The Mechanism of Microglia in the Pathogenesis of Amyotrophic Lateral Sclerosis and Its Therapeutic Strategies
ALS(amyotrophic lateral sclerosis)is a multifactorial neurodegenerative disease character-ized by the degeneration of upper and lower motor neurons leading to muscle weakness,progressive paralysis and severe functional impairment.ALS motor neuron damage is caused by a variety of factors including misfolded protein aggregation,neuroinflammation,glutamate excitotoxicity,iron overload,and demyelination.Recent studies have found that the activation of microglia is one of the important hallmarks of ALS neuropathology,but its pre-cise role in the pathogenesis of ALS remains unclear.The balance between microglia and motor neurons executes a protective effect in motor neuron damage and promotes neurogenesis.However,along the combination of genetic,environmental and other factors,stress-induced motor neuron damage is further exacerbated,concomitant with abnormal proliferation and activation of microglia.Thus,microglia not only lose their ability in motor neuron pro-tection and injury repair,but also is switched from anti-inflammation and neuroprotection to pro-inflammation and neurotoxicity in phenotype.Besides,neurotoxic signaling from motor neurons induces microglia to produce inflam-matory factors,further increases motor neuron damage,and promotes the motor neuron loss and vicious circle of cell death,thereby exacerbating the ALS progression.This review will briefly summarize and discuss the pathologi-cal role of microglia in ALS and its potential targeted therapy strategies.
NETL
NSTL
万方数据
