γ-Secretase Modulation and its Promise for Alzheimers Disease: a Medicinal Chemistry Perspective

Author(s): Ilaria Peretto, Elena La Porta.

Journal Name: Current Topics in Medicinal Chemistry

Volume 8 , Issue 1 , 2008

Become EABM
Become Reviewer

Abstract:

γ-Secretase modulation holds the promise for the development of a disease-modifying therapy for Alzheimers disease (AD). This novel concept of manipulating the cleavage specificity of the γ-secretase enzyme by pharmacological means implies that steady state levels of the potentially disease-causing amyloid-β(1-42) peptide can be lowered without the undesired side effects associated with full inhibition of this aspartyl-type protease. Following on from the initial discovery that certain non-steroidal anti-inflammatory drugs (NSAIDs) exhibit properties characteristic of γ-secretase modulators, this class of compounds has been extensively studied and exploited, leading to the discovery of NSAIDs derivatives endowed with improved potency for the reduction of amyloid-β(1-42) peptide production. In addition, a very limited number of non-NSAID derived γ-secretase modulators has also been recently claimed in the patent literature, suggesting that only a restricted number of pharmacophores might be involved in the modulation of γ-secretase.

Rights & PermissionsPrintExport Cite as


Article Details

VOLUME: 8
ISSUE: 1
Year: 2008
Page: [38 - 46]
Pages: 9
DOI: 10.2174/156802608783334097

Article Metrics

PDF: 13