Beta amyloid peptide: from different aggregation forms to the activation of different biochemical pathways.
Amyloid beta peptide (Abeta) is the major component of amyloid plaques in the brain of individuals affected by Alzheimer's disease (AD). The formation of the plaques is due to an overproduction of Abeta by APP processing, its precursor, and to its ability to convert under specific conditions from its soluble form into highly ordered fibrillar aggregates. Although neuronal degeneration occurs near the amyloid plaques, some studies have suggested that intermediates such as protofibrils or simple oligomers are also involved in AD pathogenesis and even appear to be the more dangerous species in the onset of the pathology. Further, toxic properties of aggregates of different size have been investigated and the obtained results support the hypothesis that different aggregate sizes can induce different degeneration pathways. In the present review some of the knowledge about the biochemical routes of Abeta processing and production and the relationship among Abeta and oxidative stress, metal homeostasis, inflammatory process, and cell death are summarized. Moreover, current strategies addressing both fibrillogenesis process and different Abeta altered biochemical pathways utilized for therapies are described.
Di Carlo
Marta
M
Istituto di Biomedicina ed Immunologia Molecolare, Consiglio Nazionale delle Ricerche, via Ugo La Malfa 153, Palermo, Italy. di-carlo@ibim.cnr.it
D000544:Alzheimer Disease / Q000139:chemically induced*; D000682:Amyloid / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D007249:Inflammation / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009410:Nerve Degeneration / Q000139:chemically induced*; D009474:Neurons / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D010446:Peptide Fragments / Q000378:metabolism; D058255:Protease Nexins; D011956:Receptors, Cell Surface / Q000378:metabolism; D016875:tau Proteins / Q000494:pharmacology
D000682:Amyloid; D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D010446:Peptide Fragments; D058255:Protease Nexins; D011956:Receptors, Cell Surface; D016875:tau Proteins