The Mechanism of Microglia in the Pathogenesis of Amyotrophic Lateral Sclerosis and Its Therapeutic Strategies
CHEN Youjia1, KONG Chuixi1, CAI Zhaopin1,2, SHEN Chengyong2, JIN Zhigang1*
ALS (amyotrophic lateral sclerosis) is a multifactorial neurodegenerative disease characterized 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 precise 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 protection 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 inflammatory 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 pathological role of microglia in ALS and its potential targeted therapy strategies.
CN
EN