Amyloid-β Production Via Cleavage of Amyloid-β Protein Precursor is Modulated by Cell Density
| Autor: | Jesse A. Stevenson, Rudolph E. Tanzi, Yuanlin Dong, Donna M. Romano, Andrew Browne, Zhongcong Xie, Can Zhang, Jason DiVito |
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| Rok vydání: | 2010 |
| Předmět: |
Cell Count
Enzyme-Linked Immunosorbent Assay Cleavage (embryo) Article Amyloid beta-Protein Precursor Mice Cricetulus Protein structure In vivo Cricetinae mental disorders medicine Animals Humans Protein precursor Cells Cultured Cerebral Cortex Neurons Amyloid beta-Peptides biology General Neuroscience General Medicine biology.organism_classification Peptide Fragments Protein Structure Tertiary Cell biology Molecular Weight Psychiatry and Mental health Clinical Psychology medicine.anatomical_structure Biochemistry Cell culture Cerebral cortex biology.protein Amyloid Precursor Protein Secretases Geriatrics and Gerontology Protein Processing Post-Translational Amyloid precursor protein secretase |
| Zdroj: | Journal of Alzheimer's Disease. 22:683-694 |
| ISSN: | 1875-8908 1387-2877 |
| Popis: | Mounting evidence suggests that Alzheimer's disease (AD) is caused by the accumulation of the small peptide, amyloid-β (Aβ), a proteolytic cleavage product of amyloid-β protein precursor (AβPP). Aβ is generated through a serial cleavage of AβPP by β- and γ-secretase. Aβ40 and Aβ42 are the two main components of amyloid plaques in AD brains, with Aβ42 being more prone to aggregation. AβPP can also be processed by α-secretase, which cleaves AβPP within the Aβ sequence, thereby preventing the generation of Aβ. Little is currently known regarding the effects of cell density on AβPP processing and Aβ generation. Here we assessed the effects of cell density on AβPP processing in neuronal and non-neuronal cell lines, as well as mouse primary cortical neurons. We found that decreased cell density significantly increases levels of Aβ40, Aβ42, total Aβ, and the ratio of Aβ42: Aβ40. These results also indicate that cell density is a significant modulator of AβPP processing. Overall, these findings carry profound implications for both previous and forthcoming studies aiming to assess the effects of various conditions and genetic/chemical factors, e.g., novel drugs on AβPP processing and Aβ generation in cell-based systems. Moreover, it is interesting to speculate whether cell density changes in vivo may also affect AβPP processing and Aβ levels in the AD brain. |
| Databáze: | OpenAIRE |
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