کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8686299 | 1580601 | 2018 | 48 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Alpha-synuclein deregulates the expression of COL4A2 and impairs ER-Golgi function
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موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
عصب شناسی
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چکیده انگلیسی
Alpha-synuclein (aSyn) is the major protein component of Lewy bodies and Lewy neurites, the typical pathological hallmarks in Parkinson's disease (PD) and Dementia with Lewy bodies. aSyn is capable of inducing transcriptional deregulation, but the precise effect of specific aSyn mutants associated with familial forms of PD, remains unclear. Here, we used transgenic mice overexpressing human wild-type (WT) or A30P aSyn to compare the transcriptional profiles of the two animal models. We found that A30P aSyn promotes strong transcriptional deregulation and increases DNA binding. Interestingly, COL4A2, a major component of basement membranes, was found to be upregulated in both A30P aSyn transgenic mice and in dopaminergic neurons expressing A30P aSyn, suggesting a crucial role for collagen related genes in aSyn-induced toxicity. Finally, we observed that A30P aSyn alters Golgi morphology and increases the susceptibility to endoplasmic reticulum (ER) stress in dopaminergic cells. In total, our findings provide novel insight into the putative role of aSyn on transcription and on the molecular mechanisms involved, thereby opening novel avenues for future therapeutic interventions in PD and other synucleinopathies.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neurobiology of Disease - Volume 119, November 2018, Pages 121-135
Journal: Neurobiology of Disease - Volume 119, November 2018, Pages 121-135
نویسندگان
Isabel Paiva, Gaurav Jain, Diana F. Lázaro, Kristina Gotovac JerÄiÄ, Thomas Hentrich, Cemil Kerimoglu, Raquel Pinho, Ãva M. SzegÅ, Susanne Burkhardt, Vincenzo Capece, Rashi Halder, Rezaul Islam, Mary Xylaki, Lucas A. Caldi Gomes, Anna-Elisa Roser,