Protection mechanisms against Abeta42 aggregation.
It is widely accepted that Abeta42 aggregation is a central event in the pathogenesis of Alzheimer's disease. Abeta42 oligomers and fibrils cause the breakdown of neural circuits, neuronal death and eventually dementia. There are a number of physiological molecules that can protect Abeta42 from aggregation. Promoting such protective molecules and mechanisms against Abeta42 aggregation may be a novel direction in AD drug discovery. One of the most striking protective molecules is none other than Abeta40, which inhibits Abeta42 aggregation in a specific and dosage dependent manner. Abeta40 is a critical, built-in mechanism against Abeta42 aggregation. A number of other molecules and mechanisms also inhibit Abeta42 aggregation, such as heat shock proteins, L-PGDS, heme and methionine oxidation. The relevance of these protective mechanisms to AD pathogenesis and intervention is discussed.
Yan
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Y
Biology department, Rensselear Polytechnic Institute, Troy, NY 12180, USA.
Wang
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C
D000544:Alzheimer Disease / Q000188:drug therapy / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000633:toxicity; D000818:Animals; D006801:Humans; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000494:pharmacology; D010446:Peptide Fragments / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000633:toxicity; D011487:Protein Conformation; D015398:Signal Transduction / Q000187:drug effects
D016229:Amyloid beta-Peptides; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42)