دورية أكاديمية
Macroautophagy—a novel β-amyloid peptide-generating pathway activated in Alzheimer's disease
| العنوان: | Macroautophagy—a novel β-amyloid peptide-generating pathway activated in Alzheimer's disease |
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| المؤلفون: | Yu, W. Haung, Cuervo, Ana Maria, Kumar, Asok, Peterhoff, Corrinne M., Schmidt, Stephen D., Lee, Ju-Hyun, Mohan, Panaiyur S., Mercken, Marc, Farmery, Mark R., Tjernberg, Lars O., Jiang, Ying, Duff, Karen, Uchiyama, Yasuo, Näslund, Jan, Mathews, Paul M., Cataldo, Anne M., Nixon, Ralph A. |
| المصدر: | The Journal of Cell Biology ; volume 171, issue 1, page 87-98 ; ISSN 1540-8140 0021-9525 |
| بيانات النشر: | Rockefeller University Press |
| سنة النشر: | 2005 |
| الوصف: | Macroautophagy, which is a lysosomal pathway for the turnover of organelles and long-lived proteins, is a key determinant of cell survival and longevity. In this study, we show that neuronal macroautophagy is induced early in Alzheimer's disease (AD) and before β-amyloid (Aβ) deposits extracellularly in the presenilin (PS) 1/Aβ precursor protein (APP) mouse model of β-amyloidosis. Subsequently, autophagosomes and late autophagic vacuoles (AVs) accumulate markedly in dystrophic dendrites, implying an impaired maturation of AVs to lysosomes. Immunolabeling identifies AVs in the brain as a major reservoir of intracellular Aβ. Purified AVs contain APP and β-cleaved APP and are highly enriched in PS1, nicastrin, and PS-dependent γ-secretase activity. Inducing or inhibiting macroautophagy in neuronal and nonneuronal cells by modulating mammalian target of rapamycin kinase elicits parallel changes in AV proliferation and Aβ production. Our results, therefore, link β-amyloidogenic and cell survival pathways through macroautophagy, which is activated and is abnormal in AD. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1083/jcb.200505082 |
| الإتاحة: | https://doi.org/10.1083/jcb.200505082Test https://rupress.org/jcb/article-pdf/171/1/87/1872095/jcb171187.pdfTest |
| رقم الانضمام: | edsbas.5F845C20 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1083/jcb.200505082 |
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