Beta-amyloid therapies in Alzheimer's disease.
Neurones in the brain produce beta-amyloid fragments from a larger precursor molecule termed the amyloid precursor protein (APP). When released from the cell, these protein fragments may accumulate in extracellular amyloid plaques and consequently hasten the onset and progression of Alzheimer's disease (AD). A beta fragments are generated through the action of specific proteases within the cell. Two of these enzymes, beta- and gamma-secretase, are particularly important in the formation of A beta as they cleave within the APP protein to give rise to the N-terminal and C-terminal ends of the A beta fragment, respectively. Consequently, many researchers are investigating therapeutic approaches that inhibit either beta- or gamma-secretase activity, with the ultimate goal of limiting A beta; production. An alternative AD therapeutic approach that is being investigated is to employ anti-A beta antibodies to dissolve plaques that have already formed. Both of these approaches focus on the possibility that accrual of A beta leads to neuronal degeneration and cognitive impairment characterised by AD and test the hypothesis that limiting A beta deposition in neuritic plaques may be an effective treatment for AD.
Jhee
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California Clinical Trials/Ingenix Pharmaceutical Services, 8501 Wilshire Blvd, Beverly Hills, CA 90211, USA. stan.jhee@cctrials.com
Shiovitz
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T
Crawford
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Cutler
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NR
D000544:Alzheimer Disease / Q000188:drug therapy*; D000595:Amino Acid Sequence; D053829:Amyloid Precursor Protein Secretases; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors; D010450:Endopeptidases / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D006801:Humans; D008969:Molecular Sequence Data
D016229:Amyloid beta-Peptides; D004791:Enzyme Inhibitors; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases; C509284:BACE2 protein, human; C509280:BACE1 protein, human