Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

Sci. Aging Knowl. Environ., 28 June 2006
Vol. 2006, Issue 10, p. re2
[DOI: 10.1126/sageke.2006.10.re2]

REVIEWS

Targeting the Role of the Endosome in the Pathophysiology of Alzheimer's Disease: A Strategy for Treatment

Barbara A. Tate, and Paul M. Mathews

The authors are at CNS Discovery, Global Research and Development, Pfizer Inc., Groton, CT 06234, USA (B.A.T.) and the Department of Psychiatry at the New York University School of Medicine, Center for Dementia Research, Nathan Kline Institute for Psychiatric Research, Orangeburg, NY 10962, USA (P.M.M). E-mail: barbara.tate{at}pfizer.com (B.A.T.), mathews{at}nki.rfmh.org (P.M.M.)

http://sageke.sciencemag.org/cgi/content/full/2006/10/re2

Key Words: Alzheimer's disease • amyloid • APP • endosome • Down syndrome • Niemann-Pick • secretase • cholesterol • drug discovery

Abstract: Membrane-bound endosomal vesicles play an integral role in multiple cellular events, including protein processing and turnover, and often critically regulate the cell-surface availability of receptors and other plasma membrane proteins in many different cell types. Neurons are no exception, being dependent on endosomal function for housekeeping and synaptic events. Growing evidence suggests a link between neuronal endosomal function and Alzheimer's disease (AD) pathophysiology. Endosomal abnormalities invariably occur within neurons in AD brains, and endocytic compartments are one likely site for the production of the pathogenic beta-amyloid peptide (Abeta), which accumulates within the brain during the disease and is generated by proteolytic processing of the amyloid precursor protein (APP). The enzymes and events involved in APP processing are appealing targets for therapeutic agents aimed at slowing or reversing the pathogenesis of AD. The neuronal endosome may well prove to be the intracellular site of action for inhibitors of beta-amyloidogenic APP processing. We present here the view that knowledge of the endosomal system in the disease can guide drug discovery of AD therapeutic agents.

Citation: B. A. Tate, P. M. Mathews, Targeting the Role of the Endosome in the Pathophysiology of Alzheimer's Disease: A Strategy for Treatment. Sci. Aging Knowl. Environ. 2006 (10), re2 (2006).

Read the Full Text




THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Docosahexaenoic Acid Reduces Amyloid {beta} Production via Multiple Pleiotropic Mechanisms.
M. O. W. Grimm, J. Kuchenbecker, S. Grosgen, V. K. Burg, B. Hundsdorfer, T. L. Rothhaar, P. Friess, M. C. de Wilde, L. M. Broersen, B. Penke, et al. (2011)
J. Biol. Chem. 286, 14028-14039
   Abstract »    Full Text »    PDF »



To Advertise     Find Products


Science of Aging Knowledge Environment. ISSN 1539-6150