Amyloid Inhibitors

Definition

At least 40 diseases are caused by proteins or peptides folding incorrectly and aggregating into amyloid fibrils or plaques, including Alzheimer’s disease, type II diabetes, Parkinson’s disease, Huntington’s disease, and the spongiform encephalopathies. The best-studied amyloid-based disease is Alzheimer’s, characterized pathologically by abnormally high levels of brain lesions (senile plaques), neurofibrillary tangles in dead and dying neurons, and elevated numbers of amyloid deposits in the walls of cerebral blood vessels. The major component of senile plaques is a small peptide of 39–43 amino acids called β-amyloid (Aβ). In vitro and in vivo evidence shows that soluble, oligomeric forms of Aβ have potent neurotoxic activity and are the primary causes of neuronal injury and cell death, rather than the larger fibrils and plaques that are more readily visualized. An obvious strategy to treat Alzheimer’s, and other amyloidoses, is therefore to interfere with amyloid...