NDLI: Identification of “sarsasapogenin-aglyconed” timosaponins as novel Aβ-lowering modulators of amyloid precursor protein processing

Content Provider	Royal Society of Chemistry (RSC)
Author	Leung, Chi-Ting Cao, Bei Che, Chi-Ming Liu, Yungen Kwong, Wai-Lun Sy, Lai-King Wang, Juan-Yu Lok, Chun-Nam Cheng, Lu Wan, Pui-Ki Chang, Raymond Chuen-Chung
Copyright Year	2016
Abstract	The inhibition of amyloid β (Aβ) peptide production is a key approach in the development of therapeutics for the treatment of Alzheimer's disease (AD). We have identified that timosaponins consisting of sarsasapogenin (SSG) as the aglycone can effectively lower the production of Aβ peptides and stimulate neurite outgrowth in neuronal cell cultures. Structure–activity relationship studies revealed that the cis-fused AB ring, 3β-configuration, spiroketal F-ring and 25S-configuration of SSG are the essential structural features responsible for the Aβ-lowering effects and neurite-stimulatory activity. New synthetic derivatives that retain the SSG scaffold also exhibited an Aβ lowering effect. Treatment of cells with timosaponins led to modulation of amyloid precursor protein (APP) processing through the suppression of β-cleavage and preferential lowering of the production of the 42-amino acid Aβ species (Aβ42) without affecting another γ-secretase substrate. The SSG and “SSG-aglyconed” timosaponins also penetrated brain tissue and lowered brain Aβ42 levels in mice. Our studies demonstrate that timosaponins represent a unique class of steroidal saponins that may be useful for the development of AD therapeutics.
Starting Page	3206
Ending Page	3214
Page Count	9
File Format	HTM / HTML PDF
ISSN	20416520
Volume Number	7
Issue Number	5
Journal	Chemical Science
DOI	10.1039/c5sc02377g
Language	English
Publisher	Royal Society of Chemistry
Access Restriction	Subscribed
Subject Keyword	Amyloid beta Neurite SSG Aglycone Structure\u2013activity relationship Gamma secretase Peptide Gastric acid Sarsasapogenin Amyloid precursor protein
Content Type	Text
Resource Type	Article
Subject	Chemistry

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Identification of “sarsasapogenin-aglyconed” timosaponins as novel Aβ lowering modulators of amyloid precursor protein (APP) processing

γ-Secretase modulators show selectivity for γ-secretase-mediated amyloid precursor protein intramembrane processing.

Evaluating amyloid-beta processing using novel gamma-secretase modulators in preclinical animal models

Second Generation γ-Secretase Modulators Exhibit Different Modulation of Notch β and Aβ Production

Three-amino acid spacing of presenilin endoproteolysis suggests a general stepwise cleavage of gamma-secretase-mediated intramembrane proteolysis.

β-Amyloid Precursor Protein Mutants Respond to γ-Secretase Modulators

Natural Product and Natural Product-Derived Gamma Secretase Modulators from Actaea Racemosa Extracts

The intramembrane cleavage site of the amyloid precursor protein depends on the length of its transmembrane domain.

γ-Secretase Processing and Effects of γ-Secretase Inhibitors and Modulators on Long Aβ Peptides in Cells

Identification of “sarsasapogenin-aglyconed” timosaponins as novel Aβ-lowering modulators of amyloid precursor protein processing

Similar Documents

Identification of “sarsasapogenin-aglyconed” timosaponins as novel Aβ lowering modulators of amyloid precursor protein (APP) processing

γ-Secretase modulators show selectivity for γ-secretase-mediated amyloid precursor protein intramembrane processing.

Evaluating amyloid-beta processing using novel gamma-secretase modulators in preclinical animal models

Second Generation γ-Secretase Modulators Exhibit Different Modulation of Notch β and Aβ Production

Three-amino acid spacing of presenilin endoproteolysis suggests a general stepwise cleavage of gamma-secretase-mediated intramembrane proteolysis.

β-Amyloid Precursor Protein Mutants Respond to γ-Secretase Modulators

Natural Product and Natural Product-Derived Gamma Secretase Modulators from Actaea Racemosa Extracts

The intramembrane cleavage site of the amyloid precursor protein depends on the length of its transmembrane domain.

γ-Secretase Processing and Effects of γ-Secretase Inhibitors and Modulators on Long Aβ Peptides in Cells

Identification of “sarsasapogenin-aglyconed” timosaponins as novel Aβ-lowering modulators of amyloid precursor protein processing