QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (44) Citing Articles via Google Scholar Google Scholar Articles by Nishiyama, K. Articles by Okamoto, T. Search for Related Content PubMed PubMed Citation Articles by Nishiyama, K. Articles by Okamoto, T.

 Previous Article  |  Next Article 

The Journal of Neuroscience, August 1, 1999, 19(15):6538-6548

Caveolin-3 Upregulation Activates -Secretase-Mediated Cleavage of the Amyloid Precursor Protein in Alzheimer's Disease

Kazutoshi Nishiyama¹, Bruce D. Trapp¹, Tsuneya Ikezu¹, Richard M. Ransohoff¹, Taisuke Tomita², Takeshi Iwatsubo², Ichiro Kanazawa³, Karen K. Hsiao⁴, Michael P. Lisanti⁵, and Takashi Okamoto¹

¹ Department of Neurosciences, The Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio, ² Faculty of Pharmaceutical Sciences, Tokyo University, Tokyo, Japan, ³ Division of Neuroscience, Graduate School of Medicine, Tokyo University, Tokyo, Japan, ⁴ Department of Neurology, University of Minnesota, Minneapolis, Minnesota, and ⁵ Department of Molecular Pharmacology and The Einstein Cancer Center, Albert Einstein College of Medicine, Bronx, New York

Here, we investigate the involvement of caveolins in the pathophysiology of Alzheimer's disease (AD). We show dramatic upregulation of caveolin-3 immunoreactivity in astroglial cells surrounding senile plaques in brain tissue sections from authentic AD patients and an established transgenic mouse model of AD. In addition, we find that caveolin-3 physically interacts and biochemically colocalizes with amyloid precursor protein (APP) both in vivo and in vitro. Interestingly, recombinant overexpression of caveolin-3 in cultured cells stimulated -secretase-mediated processing of APP. Immunoreactivities of APP and presenilins were concomitantly increased in caveolin-3-positive astrocytes. Because the presenilins also form a physical complex with caveolin-3, caveolin-3 may provide a common platform for APP and the presenilins to associate in astrocytes. In AD, augmented expression of caveolin-3 and presenilins in reactive astrocytes may alter APP processing, leading to the overproduction of its toxic amyloid metabolites.

Key words: Alzheimer's disease; caveolin; presenilin; amyloid precursor protein; secretase; astrocyte

---

Copyright © 1999 Society for Neuroscience  0270-6474/99/19156538-11$05.00/0

This article has been cited by other articles:

				M. I. Boulware, H. Kordasiewicz, and P. G. Mermelstein Caveolin Proteins Are Essential for Distinct Effects of Membrane Estrogen Receptors in Neurons J. Neurosci., September 12, 2007; 27(37): 9941 - 9950. [Abstract] [Full Text] [PDF]

				D. R. Wood, J. S. Nye, N. J. C. Lamb, A. Fernandez, and M. Kitzmann Intracellular Retention of Caveolin 1 in Presenilin-deficient Cells J. Biol. Chem., February 25, 2005; 280(8): 6663 - 6668. [Abstract] [Full Text] [PDF]

				S. Kametaka, M. Shibata, K. Moroe, S. Kanamori, Y. Ohsawa, S. Waguri, P. J. Sims, K. Emoto, M. Umeda, and Y. Uchiyama Identification of Phospholipid Scramblase 1 as a Novel Interacting Molecule with beta -Secretase (beta -Site Amyloid Precursor Protein (APP) Cleaving Enzyme (BACE)) J. Biol. Chem., April 18, 2003; 278(17): 15239 - 15245. [Abstract] [Full Text] [PDF]

				Y.-Y. Zhao, Y. Liu, R.-V. Stan, L. Fan, Y. Gu, N. Dalton, P.-H. Chu, K. Peterson, J. Ross Jr., and K. R. Chien Defects in caveolin-1 cause dilated cardiomyopathy and pulmonary hypertension in knockout mice PNAS, August 20, 2002; 99(17): 11375 - 11380. [Abstract] [Full Text] [PDF]

				S. V. Chochina, N. A. Avdulov, U. Igbavboa, J. P. Cleary, E. O. O'Hare, and W. G. Wood Amyloid {beta}-peptide1-40 increases neuronal membrane fluidity: role of cholesterol and brain region J. Lipid Res., August 1, 2001; 42(8): 1292 - 1297. [Abstract] [Full Text] [PDF]

				E. J. Smart, G. A. Graf, M. A. McNiven, W. C. Sessa, J. A. Engelman, P. E. Scherer, T. Okamoto, and M. P. Lisanti Caveolins, Liquid-Ordered Domains, and Signal Transduction Mol. Cell. Biol., November 1, 1999; 19(11): 7289 - 7304. [Full Text] [PDF]

				W.-Y. Park, J.-S. Park, K.-A Cho, D.-I. Kim, Y.-G. Ko, J.-S. Seo, and S. C. Park Up-regulation of Caveolin Attenuates Epidermal Growth Factor Signaling in Senescent Cells J. Biol. Chem., June 30, 2000; 275(27): 20847 - 20852. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help