Role of ABC transporters in the pathogenesis of Alzheimer's disease

ACS Chem Neurosci. 2012 Nov 21;3(11):820-31. doi: 10.1021/cn300077c. Epub 2012 Oct 11.

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disorder and the most common form of age-related dementia that begins with memory loss and progresses to include severe cognitive impairment. A major pathological hallmark of AD is the accumulation of beta amyloid peptide (Aβ) in senile plaques in the brain of AD patients. The exact mechanism by which AD takes place remains unknown. However, an increasing number of studies suggests that ATP-binding cassette (ABC) transporters, which are localized on the surface of brain endothelial cells of the blood-brain barrier (BBB) and brain parenchyma, may contribute to the pathogenesis of AD. Recent studies have unraveled important roles of ABC transporters including ABCB1 (P-glycoprotein, P-gp), ABCG2 (breast cancer resistant protein, BCRP), ABCC1 (multidrug resistance protein 1, MRP1), and the cholesterol transporter ABCA1 in the pathogenesis of AD and Aβ peptides deposition inside the brain. Therefore, understanding the mechanisms by which these transporters contribute to Aβ deposition in the brain is important for the development of new therapeutic strategies against AD. This review summarizes and highlights the accumulating evidence in the literature which describe the role of altered function of various ABC transporters in the pathogenesis and progression of AD and the implications of modulating their functions for the treatment of AD.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • ATP Binding Cassette Transporter 1
  • ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters / metabolism*
  • Alzheimer Disease / metabolism*
  • Alzheimer Disease / physiopathology
  • Amyloid beta-Peptides / metabolism*
  • Biological Transport / physiology
  • Blood-Brain Barrier / metabolism*
  • Humans
  • Neoplasm Proteins / metabolism

Substances

  • ABCA1 protein, human
  • ABCA2 protein, human
  • ABCG2 protein, human
  • ATP Binding Cassette Transporter 1
  • ATP Binding Cassette Transporter, Subfamily B, Member 1
  • ATP Binding Cassette Transporter, Subfamily G, Member 2
  • ATP-Binding Cassette Transporters
  • Amyloid beta-Peptides
  • Neoplasm Proteins