PRION BIOLOGY AND CREUTZFELDT–JAKOB DISEASE: FROM MISFOLDED PROTEINS TO CLINICAL IMPLICATIONS

Creutzfeldt–Jakob disease (CJD) is a rare, fatal, and rapidly progressive neurodegenerative disorder belonging to the group of transmissible spongiform encephalopathies, characterized by the accumulation of misfolded prion proteins (PrP^Sc) in the central nervous system. The pathogenesis involves conformational conversion of the normal cellular prion protein (PrP^C) into its pathogenic isoform, initiating a cascade of neurotoxicity, neuronal loss, and spongiform changes. CJD manifests in sporadic, genetic, and acquired forms, with clinical features including rapidly progressive dementia, myoclonus, visual disturbances, and cerebellar ataxia. Advances in diagnostic modalities—such as real-time quaking-induced conversion (RT-QuIC), magnetic resonance imaging (MRI) signal changes, and cerebrospinal fluid biomarkers—have improved early detection, yet definitive diagnosis remains postmortem through neuropathological examination. Despite intensive research, no curative therapy exists; management remains supportive, underscoring the urgency for therapeutic breakthroughs. Recent studies have explored anti-prion compounds, immunotherapeutic approaches, and gene-targeting strategies, showing promise in preclinical models. This review synthesizes current knowledge on prion biology, molecular mechanisms of disease, diagnostic advancements, and emerging therapeutic strategies, with the aim of bridging the gap between bench research and clinical application. Understanding the intricate relationship between prion protein misfolding and neurodegeneration may pave the way for targeted interventions in CJD and related prion diseases.