Misfolded protein

Misfolded proteins are not a single molecular entity but rather a class describing any protein that fails to achieve its correct three-dimensional structure. This failure can result from genetic mutations, environmental stressors, post-translational modifications, or errors during synthesis. Misfolded proteins often expose hydrophobic regions that promote aggregation into oligomers and insoluble fibrils—structures known as amyloid—which are resistant to degradation by cellular quality control systems such as the proteasome pathway. The accumulation and deposition of these aggregates disrupt cellular homeostasis and are central features in numerous diseases collectively termed "proteinopathies" or "protein conformational disorders," including neurodegenerative conditions like Alzheimer’s disease, Parkinson’s disease, prion diseases, systemic/localized amyloidoses, type 2 diabetes mellitus, some cancers, and others. Therapeutic strategies focus on stabilizing the native conformation of vulnerable proteins (e.g., tafamidis for transthyretin), reducing production or enhancing clearance of pathogenic species. However, because "misfolded protein" is a generic term encompassing many unrelated molecules with diverse sequences/functions but similar pathological folding states—and not a specific targetable molecule—it is not considered a canonical therapeutic target like an enzyme or receptor. Instead it represents a pathophysiological process underlying multiple distinct targets depending on the context.[1][2][3][4]

Other names

Protein misfoldingProtein conformational disorderProteopathyProteinopathy

Stabilization of native protein structure to prevent misfolding and aggregation; Reduction or clearance of misfolded/aggregated proteins from tissues/organs