Hiding in Plain Sight-Could a Common Molecular Mechanism Define Neurodegenerative Diseases ?

Many neurodegenerative pathologies such as Alzheimer’s (AD), Parkinson’s (PD), Huntington’s (HD), Creutzfeldt Jakob diseases (CJD) etc. are characterized by severe changes in synaptic functions and eventual neuronal death in the brain. Besides this pathological commonality, all these diseases possess a biochemical commonality in which the respective proteins aggregate to form amyloids that are known to be responsible for neuronal cell death. Amyloid formation involves the conversion of proteins from their native monomeric states (intrinsically disordered or globular) to well-organized, fibrillar aggregates in a nucleation-dependent manner. Although amyloid-diseases differ in their functional and some pathological aspects, all amyloidogenic proteins, irrespective of their native structure form a cross β-sheet structural core upon aggregation. Interestingly, the unique ability of this conformation to accommodate tightly packed interactions is reflected in its remarkable conservation among all amyloids, despite significant sequence diversity.