REPURPOSING OF ANTI-VIRAL COMPOUNDS AGAINST HDAC6 IN ALZHEIMER’S THERAPEUTICS

Abstract

There are many types of neurodegenerative disease and Alzheimer's disease (AD) is one of them that increasingly disturbs brain function and is distinguished by the buildup of abnormal proteins, neuroinflammation, and synaptic dysfunction, all of which contribute to cognitive loss. Effective therapeutic strategies for AD are still difficult to come by despite intensive research efforts. Histone deacetylase 6 (HDAC6), an enzyme intricate in protein deprivation and cellular transport procedures, has been suggested as an ideal target for AD treatment in recent investigations. Due to our limited understanding of their intricate activities and unintended side effects, the progress of particular HDAC6 inhibitors has encountered difficulties. In this context, repurposing existing anti-viral compounds as potential HDAC6 inhibitors emerge as a promising strategy. Anti-viral compounds, originally designed to combat viral infections by targeting viral replication pathways, exhibit pleiotropic effects and have been shown to modulate cellular processes beyond their primary antiviral activity. This repurposing approach provides a unique opportunity to leverage the existing knowledge and safety profiles of these compounds, expediting the translation of HDAC6-targeting therapeutics for AD treatment. The rationale behind repurposing anti-viral compounds against HDAC6 in AD lies in the shared molecular pathways implicated in both viral infections and neurodegeneration. Elimination of misfolded proteins occurs through the HDAC6, regulating immune responses, and modulating neuronal plasticity, which is dysregulated in AD. Moreover, emerging evidence suggests that viral infections can exacerbate neurodegeneration, highlighting the interplay between viral pathogenesis and neuroinflammatory processes. By repurposing anti-viral compounds as HDAC6 inhibitors, we can potentially harness their dual antiviral and neuroprotective properties, thereby mitigating the detrimental effects of viral-induced neuroinflammation in AD. In this review, we assess the potential of repurposing anti-viral drugs as inhibitors of HDAC6 in the therapy of AD. We deliver a comprehensive summary of preclinical studies investigating these drugs’ efficacy in AD animal models. Additionally, we highlight the opportunities and challenges involved in advancing these compounds into clinical trials for AD therapy. Furthermore, we emphasize the position of continued exploration to optimize vi the safety and efficiency of anti-viral drugs such as HDAC6 inhibitors in the context of AD treatment.