مرکزی صفحہ BMC Cancer Protocol for expanded indications of endoscopic submucosal dissection for early gastric cancer in... , Yin, Jie, Li, Ziyu, Ye, Yingjiang, Wei, Bo, Wang, Xin, Tian, Yantao, Li, Mengyi, Zhang, Qian, Zeng, Na, Xu, Rui, Chen, Guangyong, Zhang, Jie, Li, Peng, Cai, Jun, Yao, Hongwei, Zhang, Jun, آپ کو یہ کتاب کتنی پسند ہے؟ فائل کی کوالٹی کیا ہے؟ کوالٹی کا جائزہ لینے کے لیے کتاب ڈاؤن لوڈ کریں DOI: 10.1186/s12885-020-07312-3 ہاں چیک کریں اگر ہاں چیک کریں اگر ہاں چیک کریں اگر ہاں چیک کریں اگر آپ فائل کو کھولنے کے قابل تھے۔ فائل میں ایک کتاب ہے (مزاحیہ بھی قابل قبول ہیں) کتاب کا مواد قابل قبول ہے۔ فائل کا عنوان، مصنف اور زبان کتاب کی تفصیل سے ملتی ہے۔ دوسرے شعبوں کو نظر انداز کریں کیونکہ وہ ثانوی ہیں! نہیں چیک کریں اگر نہیں چیک کریں اگر نہیں چیک کریں اگر نہیں چیک کریں اگر
آپ کو یقین ہے کہ کتاب کا مواد ناقابل قبول ہے اور اسے بلاک کیا جانا چاہیے۔ فائل کا عنوان، مصنف یا زبان کتاب کی تفصیل سے میل نہیں کھاتی۔ دوسرے شعبوں کو نظر انداز کریں۔ This book has a different problem? Report it to us Change your answer  Together we will make our library even better Citation metadataDocument controlsMain contentAbstract : Parkinson's disease (PD) is a progressive neurodegenerative disorder that is neuropathologically characterized by degeneration of dopaminergic neurons of the substantia nigra (SN) and formation of Lewy bodies and Lewy neurites composed of aggregated [alpha]-synuclein. Proteolysis of [alpha]-synuclein by matrix metalloproteinases was shown to facilitate its aggregation and to affect cell viability. One of the proteolysed fragments, Gln79-[alpha]-synuclein, possesses a glutamine residue at its N-terminus. We argue that glutaminyl cyclase (QC) may catalyze the pyroglutamate (pGlu)79-[alpha]-synuclein formation and, thereby, contribute to enhanced aggregation and compromised degradation of [alpha]-synuclein in human synucleinopathies. Here, the kinetic characteristics of Gln79-[alpha]-synuclein conversion into the pGlu-form by QC are shown using enzymatic assays and mass spectrometry. Thioflavin T assays and electron microscopy demonstrated a decreased potential of pGlu79-[alpha]-synuclein to form fibrils. However, size exclusion chromatography and cell viability assays revealed an increased propensity of pGlu79-[alpha]-synuclein to form oligomeric aggregates with high neurotoxicity. In brains of wild-type mice, QC and [alpha]-synuclein were co-expressed by dopaminergic SN neurons. Using a specific antibody against the pGlu-modified neo-epitope of [alpha]-synuclein, pGlu79-[alpha]-synuclein aggregates were detected in association with QC in brains of two transgenic mouse lines with human [alpha]-synuclein overexpression. In human brain samples of PD and dementia with Lewy body subjects, pGlu79-[alpha]-synuclein was shown to be present in SN neurons, in a number of Lewy bodies and in dystrophic neurites. Importantly, there was a spatial co-occurrence of pGlu79-[alpha]-synuclein with the enzyme QC in the human SN complex and a defined association of QC with neuropathological structures. We conclude that QC catalyzes the formation of oligomer-prone pGlu79-[alpha]-synuclein in human synucleinopathies, which may-in analogy to pGlu-A[beta] peptides in Alzheimer's disease-act as a seed for pathogenic protein aggregation. Get Full Access Gale offers a variety of resources for education, lifelong learning, and academic research. Log in through your library to get access to full content and features! Access through your library Copyright: COPYRIGHT 2021 Springer Source CitationGale Document Number: GALE|A671783606 |
