An α2-Na/K ATPase/α-adducin complex in astrocytes triggers non–cell autonomous neurodegeneration

摘要: Perturbations of astrocytes trigger neurodegeneration in several diseases, but the glial cell-intrinsic mechanisms that induce remain poorly understood. We found a protein complex α2-Na/K ATPase and α-adducin was enriched expressing mutant superoxide dismutase 1 (SOD1), which causes familial amyotrophic lateral sclerosis (ALS). Knockdown or SOD1 protected motor neurons from degeneration, including mice vivo. Heterozygous disruption gene suppressed degeneration vivo increased lifespan mice. The pharmacological agent digoxin, inhibits Na/K activity, astrocyte-induced degeneration. Notably, were upregulated spinal cord sporadic ALS patients. Collectively, our findings define chronic activation ATPase/α-adducin as critical mechanism non-cell autonomous neurodegeneration, with implications for potential therapies neurodegenerative diseases.