CARGO RECOGNITION FAILURE IS RESPONSIBLE FOR INEFFICIENT AUTOPHAGY IN HUNTINGTON’S DISEASE
| العنوان: | CARGO RECOGNITION FAILURE IS RESPONSIBLE FOR INEFFICIENT AUTOPHAGY IN HUNTINGTON’S DISEASE |
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| المؤلفون: | Esther Wong, Zsolt Tallóczy, Esperanza Arias, Guomei Tang, Marta Martinez-Vicente, Rosa L.A. de Vries, Spike Harris, Hiroshi Koga, David Sulzer, Susmita Kaushik, Ana Maria Cuervo |
| المصدر: | Nature neuroscience |
| سنة النشر: | 2010 |
| مصطلحات موضوعية: | Serum, Huntingtin, Time Factors, animal diseases, Mutant, Apoptosis, Mitochondrion, chemistry.chemical_compound, Mice, 0302 clinical medicine, Enzyme Inhibitors, Cells, Cultured, Neurons, Serotonin Plasma Membrane Transport Proteins, 0303 health sciences, General Neuroscience, 3. Good health, Cell biology, Mice transgenic, Mitochondria, Huntington Disease, Thapsigargin, Microtubule-Associated Proteins, Immunosuppressive Agents, Subcellular Fractions, congenital, hereditary, and neonatal diseases and abnormalities, Microtubule-associated protein, Mice, Transgenic, Nerve Tissue Proteins, Biology, Article, 03 medical and health sciences, Huntington's disease, Microscopy, Electron, Transmission, mental disorders, medicine, Autophagy, Animals, Humans, Vinca Alkaloids, 030304 developmental biology, Sirolimus, medicine.disease, nervous system diseases, Disease Models, Animal, nervous system, chemistry, Hepatocytes, Lysosomes, Peptides, Neuroscience, 030217 neurology & neurosurgery |
| الوصف: | Continuous turnover of intracellular components by autophagy is necessary to preserve cellular homeostasis in all tissues. Alterations in macroautophagy, the main process responsible for bulk autophagic degradation, have been proposed to contribute to pathogenesis in Huntington's disease (HD), a genetic neurodegenerative disorder caused by an expanded polyglutamine tract in the huntingtin protein. However, the precise mechanism behind macroautophagy malfunction in HD is poorly understood. In this work, using cellular and mouse models of HD and cells from humans with HD, we have identified a primary defect in the ability of autophagic vacuoles to recognize cytosolic cargo in HD cells. Autophagic vacuoles form at normal or even enhanced rates in HD cells and are adequately eliminated by lysosomes, but they fail to efficiently trap cytosolic cargo in their lumen. We propose that inefficient engulfment of cytosolic components by autophagosomes is responsible for their slower turnover, functional decay and accumulation inside HD cells. |
| اللغة: | English |
| تدمد: | 1546-1726 1097-6256 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ce22cbfb76b4eec5bcbf546e74cc8fc6Test http://europepmc.org/articles/PMC2860687Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....ce22cbfb76b4eec5bcbf546e74cc8fc6 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15461726 10976256 |
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