RNA-Based Therapies for Neurodegenerative Diseases Targeting Pathogenic Proteins

Abstract

Neurodegeneration is featured by the gradual stagnation of neuronal function and structure, leading to significant motor and cognitive impairments. The primary histopathological features underlying these conditions include the cumulation of pathological protein aggregates, chronic inflammation, and neuronal cell death. Alzheimer's disease (AD) and Parkinson's disease (PD) are prominent examples of neurodegenerative diseases (NDDs). As of 2023, over 65 million people worldwide are affected by AD and PD, with the prevalence of these conditions steadily increasing over time. Interestingly, there are no effective therapies available to halt or slow NDD progression. Most approved treatments are focused on symptom management and are often associated with substantial side effects. Given these limitations, the development of novel therapeutic approaches targeting the molecular mechanisms underlying these disorders is essential. Notably, RNA-based therapeutics have recently emerged as a potential therapeutic approach for managing various neurological diseases, offering the potential for innovative molecular interventions in NDD. In this review, we have discussed the pathogenic role of various protein aggregates in NDD and highlighted emerging RNA-based strategies aimed at targeting these pathological proteins.