Protac technology of degrading unhealthy proteins - A futuristic approach therapy for alzheimer`s and cancer disorders

Sirisha Kodali , Monika Moorthi , Manimekalai Pichaivel

PROTAC therapy; Alzheimer's disease; Cancer; Protein degradation; Neurodegeneration; Tumorigenesis.

In recent decades, a promising therapeutic strategy called Proteolysis-Targeting Chimera (PROTAC) therapy has emerged as a potential breakthrough in the field of drug development. PROTACs are bifunctional molecules designed to degrade disease-associated proteins by harnessing the cellular machinery responsible for protein turnover. Alzheimer's disease and cancer are two devastating and prevalent diseases have limited treatment options. In Alzheimer's disease, the accumulation of misfolded proteins, such as amyloid-beta (Aβ) and tau, contributes to the neurodegenerative processes. Current therapeutic strategies for Alzheimer's disease focus on reducing the levels of these protein aggregates. Preclinical studies utilizing PROTACs against Aβ and tau have demonstrated promising results in promoting protein clearance and improving cognitive function in animal models, suggesting their therapeutic potential for Alzheimer's disease. In the realm of cancer treatment, aberrant protein expression or dysregulated signalling pathways often drive tumorigenesis. Traditional cancer therapies typically target these proteins directly. However, acquired resistance and off-target effects limit the efficacy of such treatments. PROTAC therapy provides a new avenue by inducing the degradation of disease-driving proteins, offering the advantage of targeting proteins that were previously considered "undruggable." Several PROTACs have shown efficacy in degrading oncogenic proteins, leading to tumor regression and improved outcomes in preclinical models and early-phase clinical trials. Despite the enormous potential of PROTAC therapy, several challenges remain. Optimization of PROTAC design, such as enhancing target selectivity and stability, is crucial for its successful clinical translation. Nevertheless, PROTAC therapy represents a promising and innovative strategy for the treatment of both Alzheimer's disease and cancer treatment. This review aims to provide an overview of the application of PROTAC therapy in both Alzheimer's disease and cancer, highlighting its potential as a transformative treatment approach.

Volume 8 Issue 11, November-2023

Pages : 398 - 407