SOD1, TDP-43, and Aβ protein aggregates (SOD1, TDP-43, Aβ aggregates)

SOD1, TDP-43, and Aβ protein aggregates are distinct misfolded protein assemblies found in various neurodegenerative disorders. SOD1 aggregates result from mutations in the superoxide dismutase 1 enzyme, causing familial ALS via toxic gain-of-function and disruption of cellular antioxidative defense. TDP-43 aggregates arise from abnormal cytoplasmic localization and aggregation of the TAR DNA-binding protein 43, observed in ALS and frontotemporal dementia, contributing to disease through loss of normal RNA metabolic function and gain of toxic properties. Aβ protein aggregates (amyloid-beta) are primarily associated with Alzheimer's disease, forming extracellular plaques that disrupt neuronal function and trigger inflammation. While the co-aggregation of these proteins is rarely detected in the same patient, all represent distinct but mechanistically convergent targets for drug discovery directed at mitigating neurotoxicity, preserving synaptic function, and correcting aggregation-mediated cellular dysfunction. The query combines discrete biological entities, and for proper target annotation, each protein aggregate should ideally be documented as a separate target.

Other names

Cu/Zn superoxide dismutase 1SOD1 mutant (e.g., SOD1-G93A)superoxide dismutase-1TAR DNA-binding protein 43TDP43TDP-43 fragment (e.g., TDP-25)Amyloid beta peptideAmyloid-betabeta-amyloid

Targeting these aggregates involves diverse mechanisms, including reduction of aggregate formation, enhancement of proteostasis, RNA-targeted knockdown, inhibition of aggregation, stabilization of normal protein localization, gene silencing, promotion of aggregate clearance, inhibition of fibril formation, and immunotherapy-mediated removal.