Caveolin-3 Upregulation Activates β-Secretase–Mediated Cleavage of the Amyloid Precursor Protein in Alzheimer’s Disease
| Autor: | Takeshi Iwatsubo, Richard M. Ransohoff, Taisuke Tomita, Bruce D. Trapp, Michael P. Lisanti, Ichiro Kanazawa, Tsuneya Ikezu, Karen K. Hsiao, Takashi Okamoto, Kazutoshi Nishiyama |
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| Rok vydání: | 1999 |
| Předmět: |
Caveolin 3
BACE1-AS Mice Transgenic Caveolins Article Presenilin Amyloid beta-Protein Precursor Mice Alzheimer Disease Endopeptidases Presenilin-2 mental disorders Presenilin-1 Amyloid precursor protein Animals Aspartic Acid Endopeptidases Humans Senile plaques Aged biology General Neuroscience P3 peptide Brain Membrane Proteins Recombinant Proteins Biochemistry of Alzheimer's disease Cell biology Alpha secretase Astrocytes biology.protein Amyloid Precursor Protein Secretases Neuroscience Amyloid precursor protein secretase |
| Zdroj: | The Journal of Neuroscience. 19:6538-6548 |
| ISSN: | 1529-2401 0270-6474 |
| DOI: | 10.1523/jneurosci.19-15-06538.1999 |
| Popis: | 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) bothin vivoandin vitro. Interestingly, recombinant overexpression of caveolin-3 in cultured cells stimulated β-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. |
| Databáze: | OpenAIRE |
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