Neurodegenerative diseases occur due to the progressive loss of function and death of neurons, often caused by the accumulation of misfolded proteins. Consequently, increasing the degradation of misfolded proteins and preventing cell death could be a promising treatment strategy for multiple neurodegenerative diseases.

Typically, misfolded proteins can activate ER stress, inducing a protein-unfolding response as an adaptive mechanism. If the stress becomes overwhelming, the cell undergoes apoptosis and gets eliminated. Because autophagy is a major intracellular catabolic mechanism that can promote the degradation of misfolded proteins, compounds that can activate autophagy and inhibit cell death may be able to reduce or reverse neurodegeneration.

Dr. Junying Yuan and her group have identified small molecule activators of autophagy that can promote cell survival under ER stress conditions as well as induce autophagy to inhibit neuronal cell death. The team has been investigating the mechanisms by which these molecules regulate cell survival, and they are planning to improve the potency of the compounds using medicinal chemistry and test their in vivo efficacy.