Substrate-targeting γ-secretase modulators

Thomas L. Kukar (), Thomas B. Ladd, Maralyssa A. Bann, Patrick C. Fraering, Rajeshwar Narlawar, Ghulam M. Maharvi, Brent Healy, Robert Chapman, Alfred T. Welzel, Robert W. Price, Brenda Moore, Vijayaraghavan Rangachari, Bernadette Cusack, Jason Eriksen, Karen Jansen-West, Christophe Verbeeck, Debra Yager, Christopher Eckman, Wenjuan Ye, Sarah Sagi, Barbara A. Cottrell, Justin Torpey, Terrone L. Rosenberry, Abdul Fauq, Michael S. Wolfe, Boris Schmidt, Dominic M. Walsh, Edward H. Koo and Todd E. Golde ()
Additional contact information
Thomas L. Kukar: Mayo Clinic, Mayo Clinic College of Medicine, 4500 San Pablo Road, Jacksonville, Florida 32224, USA
Thomas B. Ladd: Mayo Clinic, Mayo Clinic College of Medicine, 4500 San Pablo Road, Jacksonville, Florida 32224, USA
Maralyssa A. Bann: Mayo Clinic, Mayo Clinic College of Medicine, 4500 San Pablo Road, Jacksonville, Florida 32224, USA
Patrick C. Fraering: Brain Mind Institute and School of Life Sciences, Swiss Federal Institute of Technology (EPFL)
Rajeshwar Narlawar: Clemens Schöpf-Institute of Chemistry and Biochemistry, Technische Universitaet Darmstadt, Petersenstr. 22, D-64287 Darmstadt, Germany
Ghulam M. Maharvi: Mayo Clinic, Mayo Clinic College of Medicine, 4500 San Pablo Road, Jacksonville, Florida 32224, USA
Brent Healy: Mayo Clinic, Mayo Clinic College of Medicine, 4500 San Pablo Road, Jacksonville, Florida 32224, USA
Robert Chapman: Mayo Clinic, Mayo Clinic College of Medicine, 4500 San Pablo Road, Jacksonville, Florida 32224, USA
Alfred T. Welzel: Laboratory for Neurodegenerative Research, Conway Institute University College Dublin
Robert W. Price: Mayo Clinic, Mayo Clinic College of Medicine, 4500 San Pablo Road, Jacksonville, Florida 32224, USA
Brenda Moore: Mayo Clinic, Mayo Clinic College of Medicine, 4500 San Pablo Road, Jacksonville, Florida 32224, USA
Vijayaraghavan Rangachari: Mayo Clinic, Mayo Clinic College of Medicine, 4500 San Pablo Road, Jacksonville, Florida 32224, USA
Bernadette Cusack: Mayo Clinic, Mayo Clinic College of Medicine, 4500 San Pablo Road, Jacksonville, Florida 32224, USA
Jason Eriksen: Mayo Clinic, Mayo Clinic College of Medicine, 4500 San Pablo Road, Jacksonville, Florida 32224, USA
Karen Jansen-West: Mayo Clinic, Mayo Clinic College of Medicine, 4500 San Pablo Road, Jacksonville, Florida 32224, USA
Christophe Verbeeck: Mayo Clinic, Mayo Clinic College of Medicine, 4500 San Pablo Road, Jacksonville, Florida 32224, USA
Debra Yager: Mayo Clinic, Mayo Clinic College of Medicine, 4500 San Pablo Road, Jacksonville, Florida 32224, USA
Christopher Eckman: Mayo Clinic, Mayo Clinic College of Medicine, 4500 San Pablo Road, Jacksonville, Florida 32224, USA
Wenjuan Ye: Center for Neurologic Diseases, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
Sarah Sagi: University of California San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA
Barbara A. Cottrell: University of California San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA
Justin Torpey: University of California San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA
Terrone L. Rosenberry: Mayo Clinic, Mayo Clinic College of Medicine, 4500 San Pablo Road, Jacksonville, Florida 32224, USA
Abdul Fauq: Mayo Clinic, Mayo Clinic College of Medicine, 4500 San Pablo Road, Jacksonville, Florida 32224, USA
Michael S. Wolfe: Center for Neurologic Diseases, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
Boris Schmidt: Clemens Schöpf-Institute of Chemistry and Biochemistry, Technische Universitaet Darmstadt, Petersenstr. 22, D-64287 Darmstadt, Germany
Dominic M. Walsh: Laboratory for Neurodegenerative Research, Conway Institute University College Dublin
Edward H. Koo: University of California San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA
Todd E. Golde: Mayo Clinic, Mayo Clinic College of Medicine, 4500 San Pablo Road, Jacksonville, Florida 32224, USA

Nature, 2008, vol. 453, issue 7197, 925-929

Abstract: Alzheimer's disease: γ-secretase modulators target Aβ42 One promising approach to Alzheimer's disease treatment involves the use of drugs to reduce the rate of deposition of Aβ42, the 42-residue form of amyloid-β peptide, by curbing its generation. Certain non-steroidal anti-inflammatory drugs known as γ-secretase modulators or GSMs, including ibuprofen and sulindac, have this capacity but how they work is unclear. Now their target has been identified as a site on Aβ42 itself — rather than the presenilins or a core β-secretase component. By binding to Aβ42 these drugs inhibit not only its rate of production but also its aggregation.

Date: 2008
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/nature07055 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:453:y:2008:i:7197:d:10.1038_nature07055

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/nature07055

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().