Amyloid beta modulators and neuroprotection in Alzheimer's disease: a critical appraisal

Chandra Sekhar Kuruva; P. Hemachandra Reddy

doi:10.1016/j.drudis.2016.10.010

Amyloid beta modulators and neuroprotection in Alzheimer's disease: a critical appraisal

Chandra Sekhar Kuruva
, P. Hemachandra Reddy

Research output: Contribution to journal › Review article › peer-review

47 Scopus citations

Abstract

Multiple cellular changes have been identified as being involved in Alzheimer's disease (AD) pathogenesis, including mitochondrial damage, synaptic loss, amyloid beta (Aβ) production and/or accumulation, inflammatory responses, and phosphorylated tau formation and/or accumulation. Studies have established that Aβ-induced synaptic dysfunction is dependent on abnormal amyloid precursor protein (APP) processing caused by β- and γ-secretases, resulting in the generation of Aβ. The Aβ formed as a result of abnormal APP processing induces phosphorylated tau and activates glycogen synthase kinase-3β (GSK3β) and cyclin-dependent kinase-5 (CDK5). Here, we review the latest research on the development of Aβ modulators for neuroprotection in AD. We also review the use of molecular inhibitors as therapeutic targets in AD.

Original language	English (US)
Pages (from-to)	223-233
Number of pages	11
Journal	Drug Discovery Today
Volume	22
Issue number	2
DOIs	https://doi.org/10.1016/j.drudis.2016.10.010
State	Published - Feb 1 2017

Funding

Work presented in this article is supported by NIH grants AG042178, AG047812 and the Garrison Family Foundation.

Funders	Funder number
Garrison Family Foundation
Author National Institutes of Health National Institutes of Health National Institutes of Health National Institutes of Health The Bev Hartig Huntington's Disease Foundation National Institutes of Health	AG047812
National Institute of Aging	R01AG042178

ASJC Scopus subject areas

Pharmacology
Drug Discovery

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10.1016/j.drudis.2016.10.010

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abstract = "Multiple cellular changes have been identified as being involved in Alzheimer's disease (AD) pathogenesis, including mitochondrial damage, synaptic loss, amyloid beta (Aβ) production and/or accumulation, inflammatory responses, and phosphorylated tau formation and/or accumulation. Studies have established that Aβ-induced synaptic dysfunction is dependent on abnormal amyloid precursor protein (APP) processing caused by β- and γ-secretases, resulting in the generation of Aβ. The Aβ formed as a result of abnormal APP processing induces phosphorylated tau and activates glycogen synthase kinase-3β (GSK3β) and cyclin-dependent kinase-5 (CDK5). Here, we review the latest research on the development of Aβ modulators for neuroprotection in AD. We also review the use of molecular inhibitors as therapeutic targets in AD.",

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Amyloid beta modulators and neuroprotection in Alzheimer's disease: a critical appraisal

Abstract

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