CHEMICAL BIOLOGY APPROACHES TO MODULATE PROTEASOMAL ACTIVITY

 The study of proteasome is a rapidly evolving field with multifaceted implications in neuroscience, aging, and cancer. Recent developments structural biology of the proteasome machinery has catapulted the drug discovery and targeted protein degradation. The success of proteasome inhibitors like Bortezomib and Ixazomib has also led to new interests in developing more precise inhibitors for the various proteasome isoforms. Proteasome activation is a relatively new field, and much has to be done in the field. The 20S CP is an emerging target in chemical biology and drug discovery for its implications in maintaining protein homeostasis and immune regulation. The central theme of the thesis is to study the proteasome in cellular contexts to develop new chemical biology tools to study the proteasome and its modulation by small molecules and probes in cellular contexts to ameliorate protein accumulation-mediated neurodegeneration