Protein aggregation in the brain: the molecular basis for Alzheimer's and Parkinson's diseases

Mol Med. 2008 Jul-Aug;14(7-8):451-64. doi: 10.2119/2007-00100.Irvine.


Developing effective treatments for neurodegenerative diseases is one of the greatest medical challenges of the 21st century. Although many of these clinical entities have been recognized for more than a hundred years, it is only during the past twenty years that the molecular events that precipitate disease have begun to be understood. Protein aggregation is a common feature of many neurodegenerative diseases, and it is assumed that the aggregation process plays a central role in pathogenesis. In this process, one molecule (monomer) of a soluble protein interacts with other monomers of the same protein to form dimers, oligomers, and polymers. Conformation changes in three-dimensional structure of the protein, especially the formation of beta-strands, often accompany the process. Eventually, as the size of the aggregates increases, they may precipitate as insoluble amyloid fibrils, in which the structure is stabilized by the beta-strands interacting within a beta-sheet. In this review, we discuss this theme as it relates to the two most common neurodegenerative conditions-Alzheimer's and Parkinson's diseases.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alzheimer Disease / diagnosis
  • Alzheimer Disease / epidemiology
  • Alzheimer Disease / etiology*
  • Alzheimer Disease / metabolism
  • Amyloid beta-Peptides / metabolism*
  • Amyloid beta-Peptides / physiology
  • Amyloid beta-Peptides / toxicity
  • Brain / metabolism*
  • Brain / pathology
  • Humans
  • Incidence
  • Models, Biological
  • Parkinson Disease / diagnosis
  • Parkinson Disease / epidemiology
  • Parkinson Disease / etiology*
  • Parkinson Disease / metabolism
  • Plaque, Amyloid / metabolism*
  • alpha-Synuclein / metabolism
  • alpha-Synuclein / physiology


  • Amyloid beta-Peptides
  • alpha-Synuclein