Post-Covid Alzheimer and Its Remediation via PROTACs Therapy: A Comprehensive Review

Area of Science:

• Neuroscience
• Immunology
• Pharmacology

Background:

• Alzheimer's disease (AD) is a progressive neurodegenerative disorder marked by memory loss and cognitive decline, linked to amyloid-β and tau pathology.
• Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) impacts the central nervous system, potentially accelerating neurodegeneration and exacerbating AD.
• Emerging evidence links COVID-19 to increased tau hyperphosphorylation, a key feature of AD.

Purpose of the Study:

• To review current knowledge on the interactions between COVID-19 and Alzheimer's disease.
• To evaluate proteolysis-targeting chimeras (PROTACs) as a potential therapeutic strategy for AD.

Main Methods:

• A narrative synthesis of recent literature was conducted.
• The review focused on SARS-CoV-2 neuropathology, tau pathology in AD, and PROTAC development.
• The ubiquitin-proteasome system's role in PROTAC-mediated protein degradation was examined.

Main Results:

• COVID-19 infection can precipitate or worsen neurodegenerative processes, including increased tau phosphorylation.
• Conventional AD therapies have limited efficacy.
• PROTACs, which induce protein degradation, show preclinical promise for targeting pathogenic proteins in AD, including tau.

Conclusions:

• COVID-19 may intensify AD pathogenesis via tau hyperphosphorylation, necessitating targeted interventions.
• PROTACs represent a novel protein-degradation approach with potential for treating tau-mediated AD.
• Further preclinical and clinical studies are essential to validate PROTACs' efficacy and safety in AD treatment.