Microglia centered pathogenesis in ALS: insights in cell interconnectivity.

摘要: Amyotrophic lateral sclerosis (ALS) is the most common and aggressive form of adult motor neuron (MN) degeneration. The cause disease still unknown, but some protein mutations have been linked to pathological process. Loss upper lower MNs results in progressive muscle paralysis ultimately death due respiratory failure. Although initially thought derive from selective loss MNs, pathogenic concept non-cell-autonomous has come forefront for contribution glial cells ALS, particular microglia. Recent studies suggest that microglia may a protective effect on MN an early stage. Conversely, activated contribute enhance by secreting neurotoxic factors, impaired microglial function at end-stage instead accelerate progression. However, nature microglial-neuronal interactions lead degeneration remains elusive. We review neurodegenerative network ALS pathology, with special focus each cell type data obtained transgenic SOD1G93A rodents, widely used model. further discuss diverse roles neuroinflammation phenotypes modulation pathology. provide information processes associated dysfunctional cell-cell communication summarize findings cross-talk between neurons astroglia, microglia, as well spread factors. also highlight relevance neurovascular disruption exosome trafficking harmful beneficial influences NG2 cells, oligodendrocytes Schwann will be discussed well. Insights into complex intercellular perturbations underlying including target identification, our efforts develop effective therapeutic approaches preventing or reversing symptomatic progression this devastating disease.