Neurodegenerative aspects of protein aggregation

Abstract

Protein aggregation and amyloid fibril deposits are characteristic features of more than twenty pathologic conditions characterized by plaque deposition in the central nervous system. Recent studies point out relationships between protein misfolding and numerous serious diseases. Despite different origins (sporadic, familial or transmissible), they are sometimes called conformational diseases to emphasize aberrant conformations as the putative cause of deposits that precede or accompany the clinical manifestation of the disease. Neurological disorders such as Alzheimer's disease (AD), Prion disorders (PrD), Parkinson's disease (PD), and Huntington's disease (HD) are the most typical examples of protein-based dementias, characterized by protein conformational transitions (α-helix/random coil to β-sheet) that cause aggregation followed by fibrillization. Although it is very tempting to postulate a common mechanism of toxicity based on conformational and structural analogies, it should be noted that the factors responsible for conformational transition, oligomerization, aggregation, and plaque formation, are still subject of speculation and additional data is required to test the amyloid fibril hypothesis.