A small-molecule stabilizer of the calpastatin-calpain-2 complex restores mitochondrial function and mitigates neurodegeneration - PubMed
4 hours ago
- #calpain
- #neurodegeneration
- #mitochondria
- A36, derived from CHIR99021, is a brain-penetrant small molecule that stabilizes the CAST-calpain-2 complex, limiting calpain-2 activation and mitochondrial damage.
- In HD and tauopathy models, A36 normalized mitochondrial function, reduced oxidative stress, and improved neuron survival.
- In vivo studies in R6/2 HD and PS19 tauopathy mice showed A36 reduced neurodegeneration, protein aggregation, and behavioral deficits.
- Pharmacological stabilization of the CAST-calpain-2 complex is proposed as a therapeutic strategy for neurodegenerative diseases.