Decoding Protein Misfolding: Advances In Prion Disease Pathogenesis, Biomarker Discovery, And Therapeutic Development

Prion diseases are among the class of transmissible neurodegenerative disorders that are universally fatal, and any disease mechanism involving misfolding of the native prion protein (PrP^C) into a pathogenic isoform (PrP^Sc). Examples of such disease states include Creutzfeldt-Jakob disease (CJD) and fatal familial insomnia (FFI), characterized by rapid clinical decline, frequent phenotypic variation, and an absence of disease-modifying therapies. Even though more and more people around the world are working on research about prion diseases, India still doesn't recognize them very well because of limited diagnostic tools, scattered epidemiologic evidence, and a lack of clinical awareness. There is no centralized or coordinated surveillance for cases of prion disease that can perform molecular diagnostics, which makes it hard to find and report these diseases quickly. This review summarizes the latest progress in prion biology and translational research, focusing on gene- and RNA-based therapies, AI-assisted diagnostic tools, and how findings from cross-disease proteinopathy studies relate to prion diseases. The review also discusses an integrative framework for India that utilizes genomic context, promotes amplifying growth through partnerships with institutions, and focuses on policy-level investment in the current advancements in precision medicine infrastructure.