Academic Journal
Role of P2X7 and P2Y2 receptors on α-secretase-dependent APP processing: Control of amyloid plaques formation “in vivo” by P2X7 receptor
| العنوان: | Role of P2X7 and P2Y2 receptors on α-secretase-dependent APP processing: Control of amyloid plaques formation “in vivo” by P2X7 receptor |
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| المؤلفون: | M. Teresa Miras-Portugal, Juan I. Diaz-Hernandez, Rosa Gomez-Villafuertes, Miguel Diaz-Hernandez, Antonio R. Artalejo, Javier Gualix |
| المصدر: | Computational and Structural Biotechnology Journal, Vol 13, Iss C, Pp 176-181 (2015) |
| بيانات النشر: | Elsevier |
| سنة النشر: | 2015 |
| المجموعة: | Directory of Open Access Journals: DOAJ Articles |
| مصطلحات موضوعية: | Alzheimer's disease, APP processing, α-Secretase, GSK-3, P2X7 receptor, P2Y2 receptor, Biotechnology, TP248.13-248.65 |
| الوصف: | Amyloid precursor protein (APP) is expressed in a large variety of neural and non-neural cells. The balance between non-pathogenic and pathologic forms of APP processing, mediated by α-secretase and β-secretase respectively, remains a crucial step to understand β-amyloid, Aβ42 peptide, formation and aggregation that are at the origin of the senile plaques in the brain, a characteristic hallmark of Alzheimer's disease (AD). In Neuro-2a, a neuroblastoma cell line that constitutively expresses APP, activation of the P2X7 receptor leads to reduction of α-secretase activity, the opposite effect being obtained by P2Y2 receptor activation. The in vivo approach was made possible by the use of J20 mice, a transgenic mouse model of familial Alzheimer's disease (FAD) expressing human APP mutant protein. This animal exhibits prominent amyloid plaques by six months of age. In vivo inhibition of the P2X7 receptor induced a significant decrease in the number and size of hippocampal amyloid plaques. This reduction is mediated by an increase in the proteolytic processing of APP through α-secretase activity, which correlates with an increase in the phosphorylated form of GSK-3, a less active form of this enzyme. The in vivo findings corroborate the therapeutic potential of P2X7 antagonists in the treatment of FAD. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| ردمك: | 978-2-00-103701-8 2-00-103701-5 |
| تدمد: | 2001-0370 |
| Relation: | http://www.sciencedirect.com/science/article/pii/S2001037015000094; https://doaj.org/toc/2001-0370; https://doaj.org/article/30d6092cc8e444649b235bdcdcfcd5f5 |
| DOI: | 10.1016/j.csbj.2015.02.005 |
| الاتاحة: | https://doi.org/10.1016/j.csbj.2015.02.005 https://doaj.org/article/30d6092cc8e444649b235bdcdcfcd5f5 |
| رقم الانضمام: | edsbas.35D19717 |
| قاعدة البيانات: | BASE |
Full Text Finder | ردمك: | 9782001037018 2001037015 |
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| تدمد: | 20010370 |
| DOI: | 10.1016/j.csbj.2015.02.005 |