Fig. 9.

Summary of pathological and phenotypic progression in ANXA11-P36R knock-in ALS mice. The pathological and phenotypic progression in ANXA11-P36R knock-in ALS mice is characterized by early abnormal protein aggregation, motor neuron degeneration, neuroinflammation, and autophagy deficits. At 2 months, abnormal protein aggregates were detected in the central nervous system and muscles, accompanied by spontaneous electromyographic activity. Mutant ANXA11 translocated from the nucleus to the perinuclear region, co-aggregating with p62 and TDP-43. Motor neuron degeneration, including neuronal loss and morphological changes, became pronounced by 9 months, alongside neuroinflammation marked by glial activation and NF-κB translocation. Autophagy deficits, indicated by decreased levels of BECN1 and LC3BII/I, were synchronous with motor decline. Muscle atrophy began to appear from 9-months on and was evident by 12 months, though ANXA11-mutant mice survived beyond 24 months