TARDBP and proteostasis deficiencies: There was a downregulation of homeostatic genes and an increase in neurodegenerative genes in microglia after antibiotic treatment, and the microglia signature change preceded changes in motor function.359 Grn loss of function promoted the microglial transition from a homeostatic to a disease-specific state, aggravated TDP-43 pathology and neurodegeneration through the synergy of microglia and the complement system since deleting the genes for C1qa and C3 mitigated microglial toxicity and rescued TDP-43 proteinopathy and neurodegeneration.360