In Creutzfeldt-Jakob disease (CJD), the hallmark neuropathological triad includes spongiform change, neuronal loss, and reactive gliosis. The infectious prion protein (PrPSc) causes disease by:

• A Converting normal cellular PrPc to the abnormal beta-sheet-rich PrPSc conformation by direct protein-protein contact ✓
• B Encoding a novel nucleic acid genome distinct from host DNA
• C Activating toll-like receptors to induce inflammatory neurodegeneration
• D Inserting into the mitochondrial membrane causing cytochrome c release

Explanation

Prions (PrPSc) are misfolded isoforms of the normal cellular prion protein PrPc that share identical amino acid sequence but adopt an abnormal beta-sheet-rich (aggregation-prone) tertiary structure. PrPSc propagates by directly binding to and inducing conformational conversion of normal PrPc to PrPSc — a self-templating (seeded polymerization) mechanism requiring no nucleic acid. The accumulation of protease-resistant PrPSc aggregates in neurons causes spongiform vacuolation and cell death through incompletely understood mechanisms.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.