Microglial contribution to neurodegeneration within the CNS and inflammation-independent degeneration within the PNS in the SOD1 (G93A) mouse model for ALS – a 2P-LSM study in vivo

Introduction: Amyotrophic lateral sclerosis (ALS) is an adult-onset neurological disorder, characterized by progressive loss of motor neurons and degeneration of pyramidal tracts. Mutations in the enzyme superoxide dismutase (SOD1) are the most frequent cause of inherited ALS. Transgenic mice expressing various ALS-linked mutations in SOD1 (mSOD1) recapitulate the fatal paralysis seen in human patients. The mSOD1-mediated toxicity is shown to be non-cell-autonomous deriving not only from motor neurons. In particular, microglia and astrocytes substantially contribute to disease progression. The impact of neuroinf…