Amyloidogenic protein

Amyloidogenic proteins and peptides are a diverse group of proteins that undergo a conformational transition from their functional, soluble states into insoluble, highly ordered fibrillar aggregates known as amyloids [1]. These aggregates are characterized by a cross-beta sheet quaternary structure and are the hallmark of various diseases collectively known as amyloidoses, including Alzheimer's disease, Parkinson's disease, and transthyretin amyloidosis [2]. In these conditions, the accumulation of misfolded proteins like amyloid-beta, tau, alpha-synuclein, or transthyretin leads to proteotoxicity, tissue damage, and organ dysfunction [1, 2]. Therapeutic strategies targeting these proteins involve stabilizing the native conformation (kinetic stabilizers), inhibiting the aggregation process, or utilizing immunotherapy to clear established plaques [3, 4]. Despite the clinical success of some anti-amyloid agents, challenges such as the risk of Amyloid-Related Imaging Abnormalities (ARIA) and the difficulty of targeting specific toxic oligomeric species persist [3].

Other names

Amyloid-forming proteinMisfolded proteinAmyloid peptideAmyloid fibril proteinProteotoxic aggregate

Mechanisms include kinetic stabilization of the native protein state to prevent misfolding, inhibition of protein aggregation, and monoclonal antibody-mediated clearance of existing amyloid deposits.