Academic Journal
Fibrillar prion peptide PrP (106-126) treatment induces Dab1 phosphorylation and impairs APP processing in and Aβ production in cortical neurons
| العنوان: | Fibrillar prion peptide PrP (106-126) treatment induces Dab1 phosphorylation and impairs APP processing in and Aβ production in cortical neurons |
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| المؤلفون: | Gavin, Rosalina, Urena, Jesus, Rangel, Alejandra (R17729), Pastrana, Miguel A., Requena, Jesus R., Soriano, Eduardo, Aguzzi, Adriano, Rio, Jose A. del |
| بيانات النشر: | U.S., Academic Press |
| سنة النشر: | 2008 |
| المجموعة: | University of Western Sydney (UWS): Research Direct |
| مصطلحات موضوعية: | 060602 - Animal Physiology - Cell, prions, nervous system, diseases, amyloidosis, oxidative stress |
| الوصف: | Alzheimer's disease and prion diseases (e.g., Creutzfeldt-Jakob disease) display profound neural lesions associated with aberrant protein processing and extracellular amyloid deposits. However, the intracellular events in prion diseases and their relation with the processing of the amyloid precursor protein (APP) and β-amyloid generation are unknown. The adaptor protein Dab1 may regulate intracellular trafficking and secretase-mediated proteolysis in APP processing. However, a putative relationship between prion diseases and Dab1/APP interactions is lacking. Thus, we examined, in inoculated animals, whether Dab1 and APP processing are targets of the intracellular events triggered by extracellular exposure to PrP(106-126) peptide. Our in vitro results indicate that PrP(106-126) peptide induces tyrosine phosphorylation of Dab1 by activated members of the Src family of tyrosine kinases (SFK), which implies further Dab1 degradation. We also corroborate these results in Dab1 protein levels in prion-inoculated hamsters. Finally, we show that fibrillary prion peptides have a dual effect on APP processing and β-amyloid production. First, they block APP trafficking at the cell membrane, thus decreasing β-amyloid production. In parallel, they reduce Dab1 levels, which also alter APP processing. Lastly, neuronal cultures from Dab1-deficient mice showed severe impairment of APP processing with reduced sAPP secretion and Aβ production after prion peptide incubation. Taken together, these data indicate a link between intracellular events induced by exposure to extracellular fibrillary peptide or PrPres, and APP processing and implicate Dab1 in this link. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | |
| اللغة: | English |
| Relation: | Neurobiology of Disease--0969-9961--1095-953X Vol. 30 Issue. 2 pp: 243-254 |
| DOI: | 10.1016/j.nbd.2008.02.001 |
| الاتاحة: | http://handle.uws.edu.au:8081/1959.7/uws:32545 https://doi.org/10.1016/j.nbd.2008.02.001 |
| رقم الانضمام: | edsbas.951C1B50 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1016/j.nbd.2008.02.001 |
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