CA77.1 [CMA Activator]

CA77.1 is a novel selective chaperone-mediated autophagy (CMA) activator by increasing the expression of the lysosomal receptor for this pathway, LAMP2A, in lysosomes. Chaperone-mediated autophagy (CMA), is a selective autophagy shown to degrade neurodegeneration-related proteins such as alpha-synuclein (alpha-syn) or tau. Loss of neuronal CMA leads to altered neuronal function, selective changes in the neuronal metastable proteome and proteotoxicity. Chemical upregulation of CMA has been shown to ameliorate pathology in AD experimental mouse models, reduce brain pathology and improve disease phenotype. CA77.1 is able to activate CMA in vitro and in vivo (in contrary to it's derivative AR7 which was not suitable for in vivo application). CA77.1 is able to activate CMA in vivo, and demonstrates brain penetrance and favorable pharmacokinetics. It has been shown in animal studies that administration of CA77.1 to enhance chaperone-mediated autophagy, may help to degrade toxic pathogenic protein products such as tau proteins and has potential applications in the treatment of Alzheimer's disease.