Proteins involved in amyloidosis

Amyloidosis refers to a group of rare, serious diseases caused by the extracellular accumulation of misfolded proteins that aggregate into insoluble, beta-pleated sheet fibrils known as amyloid. These proteins, which include Amyloid-beta (Abeta), Transthyretin (TTR), Immunoglobulin light chains (AL), and Serum amyloid A (SAA), are normally soluble but undergo conformational changes due to genetic mutations, aging, or chronic inflammation. The deposition of these fibrils disrupts the architecture and function of vital organs such as the heart, kidneys, and brain, leading to systemic or localized pathology. Therapeutic interventions are highly protein-specific, targeting the precursor protein synthesis (e.g., RNA interference for TTR), stabilizing the protein's native state (e.g., kinetic stabilizers for TTR), or utilizing monoclonal antibodies to clear existing plaques (e.g., anti-Abeta antibodies in Alzheimer's disease). Understanding the specific proteostatic failure for each protein is critical for developing effective disease-modifying treatments.

Other names

Amyloidogenic proteinsAmyloid-forming proteinsAmyloid precursor proteinsMisfolded proteins

Kinetic stabilization of protein tetramers, RNA interference (RNAi) mediated knockdown of protein synthesis, Antisense oligonucleotide (ASO) mediated mRNA degradation, Monoclonal antibody-mediated fibril/plaque clearance, and inhibition of fibril polymerization.