Abstract
Treating Alzheimers disease (AD) is one of todays biggest unmet medical needs. The drugs currently available transiently relieve some symptoms but have no significant effects on the progression of the disease. Progress in the past decade suggests that the amyloidogenesis of the inactive monomeric amyloid β peptide (Aβ) into a subset of toxic Aβ polymers is responsible for neurodegeneration in AD. Not all forms of Aβ aggregates are damaging, for there are patients whose brains accumulated large amounts of Aβ in the form of plaques, but they had no obvious neurodegeneration and symptoms of dementia. Since Aβ can polymerize into many types of polymers or aggregates, the form of Aβ that induces neurodegeneration in AD, defined here as bioactive Aβ, is not clear. Preventing the formation of bioactive Aβ or inactivating previously formed bioactive Aβ is a promising approach for treating AD. This review describes our efforts to develop a cell-based assay for detecting bioactive Aβ, to verify the concept of bioactive Aβ in an animal model of AD and in post mortem brain tissue from AD patients, and to use this assay to screen for drugs that can inactivate bioactive Aβ. These studies show the proof in principle that inactivating bioactive Aβ is a promising approach to treat AD. Several promising compounds that can inactivate bioactive Aβ species are also described.
Keywords: Alzheimer's disease, amyloid β peptide, amyloidogenesis, bioactive amyloid species, MTT, drug screening
Current Alzheimer Research
Title: Treating Alzheimers Disease by Inactivating Bioactive Amyloid β Peptide
Volume: 3 Issue: 2
Author(s): Yuanbin Liu and David Schubert
Affiliation:
Keywords: Alzheimer's disease, amyloid β peptide, amyloidogenesis, bioactive amyloid species, MTT, drug screening
Abstract: Treating Alzheimers disease (AD) is one of todays biggest unmet medical needs. The drugs currently available transiently relieve some symptoms but have no significant effects on the progression of the disease. Progress in the past decade suggests that the amyloidogenesis of the inactive monomeric amyloid β peptide (Aβ) into a subset of toxic Aβ polymers is responsible for neurodegeneration in AD. Not all forms of Aβ aggregates are damaging, for there are patients whose brains accumulated large amounts of Aβ in the form of plaques, but they had no obvious neurodegeneration and symptoms of dementia. Since Aβ can polymerize into many types of polymers or aggregates, the form of Aβ that induces neurodegeneration in AD, defined here as bioactive Aβ, is not clear. Preventing the formation of bioactive Aβ or inactivating previously formed bioactive Aβ is a promising approach for treating AD. This review describes our efforts to develop a cell-based assay for detecting bioactive Aβ, to verify the concept of bioactive Aβ in an animal model of AD and in post mortem brain tissue from AD patients, and to use this assay to screen for drugs that can inactivate bioactive Aβ. These studies show the proof in principle that inactivating bioactive Aβ is a promising approach to treat AD. Several promising compounds that can inactivate bioactive Aβ species are also described.
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Cite this article as:
Liu Yuanbin and Schubert David, Treating Alzheimers Disease by Inactivating Bioactive Amyloid β Peptide, Current Alzheimer Research 2006; 3 (2) . https://dx.doi.org/10.2174/156720506776383077
DOI https://dx.doi.org/10.2174/156720506776383077 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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