Genetic and pharmacological basis for therapeutic inhibition of beta- and gamma-secretases in mouse models of Alzheimer's memory deficits.

Genetic and pharmacological basis for therapeutic inhibition of beta- and gamma-secretases in mouse models of Alzheimer's memory deficits. Research Abstract Details 

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Genetic and pharmacological basis for therapeutic inhibition of beta- and gamma-secretases in mouse models of Alzheimer's memory deficits. Abstract Text:

Masuo Ohno,

Alzheimer's disease (AD) is a dementing neurodegenerative disorder for which effective disease-modifying therapeutic treatments have not yet been developed. Genetic and molecular biological studies provide accumulating evidence supporting the hypothesis that the production of amyloid-beta (Abeta) peptides, especially neurotoxic Abeta42, is central to the pathophysiology of AD--the 'amyloid cascade' hypothesis. Abeta is proteolytically generated from a type I integral membrane amyloid precursor protein by the sequential action of two enzymes, called beta- and gamma-secretase, in reference to their cleavage sites at the N- and C-terminals, respectively. Given the strong association between Abeta and AD, the strategies to inhibit the production of Abeta, the first step of the amyloid cascade, should prove beneficial as truly disease-modifying therapeutic approaches for the treatment of AD. Recent advances in genetic strategies including knockouts, transgenics and virus-delivered small interfering RNAs and the development of potent and specific small-molecule inhibitors have opened a new window to test the impacts of beta- and gamma-secretase inhibition in vivo. Since cognitive deficits are at the heart of AD, one of the most important challenges is to determine the therapeutic potential of secretase-inhibiting approaches for AD-related memory deficits, linking perspectives through the prism of molecular/pathological events and those through behavioral and neurophysiological manifestations. I review recent progress in this field, with special focus on the functional consequences of beta- and gamma-secretase inhibition and altered amyloid neuropathology in mouse models of AD memory deficits.

Genetic and pharmacological basis for therapeutic inhibition of beta- and gamma-secretases in mouse models of Alzheimer's memory deficits. Publishing Authors By Initials

M Ohno,

For similar genetic processes: gene expression regulation: epigenesis, genetic: gene silencing: rna interference research abstracts see: genetic processes: gene expression regulation: epigenesis, genetic: gene silencing: rna interference research

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Genetic and pharmacological basis for therapeutic inhibition of beta- and gamma-secretases in mouse models of Alzheimer's memory deficits. Journal Published:

PUBLICATION TYPE: Review

Journal: Reviews in the neurosciences

VOLUME: 17

Page Numbers: 429-54

Journal Abbreviation:

ISSN: 0334-1763

DAY: 3

MONTH: 12

YEAR: 2006

Genetic and pharmacological basis for therapeutic inhibition of beta- and gamma-secretases in mouse models of Alzheimer's memory deficits. Information

Number of References: 146

LANGUAGE: eng

NlmUniqueID: 8711016

Genetic and pharmacological basis for therapeutic inhibition of beta- and gamma-secretases in mouse models of Alzheimer's memory deficits. Keywords Mesh Terms:

KEYWORDS: RNA Interference

MESH TERMS: physiology

Chemical & Substance for Abstract: Genetic and pharmacological basis for therapeutic inhibition of beta- and gamma-secretases in mouse models of Alzheimer's memory deficits. Information

Substance Name: Bace1 protein, mouse

Registry Number: EC 3.4.23.46

Grant and Affiliation Information for Genetic and pharmacological basis for therapeutic inhibition of beta- and gamma-secretases in mouse models of Alzheimer's memory deficits.

AFFILIATION: Department of Physiology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA. mohno@nki.rfmh.org

Country: England

AGENCY: United States NIMH

GRANT: R01MH067251

ACRONYM: MH

MEDLINETA: Rev Neurosci

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