Seeded assembly in vitro does not replicate the structures of α‐synuclein filaments from multiple system atrophy
| العنوان: | Seeded assembly in vitro does not replicate the structures of α‐synuclein filaments from multiple system atrophy |
|---|---|
| المؤلفون: | Michel Goedert, Masato Hasegawa, Airi Tarutani, Takashi Ando, Sofia Lövestam, Tomoyasu Matsubara, Mari Yoshida, Taisuke Tomita, Manuel Schweighauser, Kazuko Hasegawa, Sjors H.W. Scheres, Shigeo Murayama |
| المصدر: | FEBS Open Bio, Vol 11, Iss 4, Pp 999-1013 (2021) FEBS Open Bio |
| بيانات النشر: | Wiley, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, Amyloid, Protein Conformation, animal diseases, multiple system atrophy, Protein Aggregation, Pathological, General Biochemistry, Genetics and Molecular Biology, law.invention, Protein filament, Protein Aggregates, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Atrophy, law, mental disorders, medicine, Humans, lcsh:QH301-705.5, Research Articles, Alpha-synuclein, cryo electron microscopy, Molecular Structure, Dementia with Lewy bodies, Putamen, Brain, food and beverages, amyloid, medicine.disease, In vitro, Cell biology, nervous system diseases, 030104 developmental biology, alpha‐synuclein, chemistry, nervous system, lcsh:Biology (General), 030220 oncology & carcinogenesis, alpha-Synuclein, Recombinant DNA, Protein Binding, Research Article |
| الوصف: | The propagation of conformational strains by templated seeding is central to the prion concept. Seeded assembly of α‐synuclein into filaments is believed to underlie the prion‐like spreading of protein inclusions in a number of human neurodegenerative diseases, including Parkinson's disease, dementia with Lewy bodies (DLB) and multiple system atrophy (MSA). We previously determined the atomic structures of α‐synuclein filaments from the putamen of five individuals with MSA. Here, we used filament preparations from three of these brains for the in vitro seeded assembly of recombinant human α‐synuclein. We find that the structures of the seeded assemblies differ from those of the seeds, suggesting that additional, as yet unknown, factors play a role in the propagation of the seeds. Identification of these factors will be essential for understanding the prion‐like spreading of α‐synuclein proteinopathies. The assembly of certain proteins into amyloids underlies multiple neurodegenerative diseases. The spreading of these assemblies through the brain is thought to occur through a prion‐like mechanism. We used filaments extracted from multiple system atrophy brains to seed recombinant α‐synuclein. The resulting structures differ from those of the seeds, indicating that seeded assembly does not necessarily replicate the seed structures. |
| اللغة: | English |
| تدمد: | 2211-5463 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9e5dfb5ecd75f99dc6133477696ddd1cTest https://doaj.org/article/35585117288f416087b434934b3a4a26Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....9e5dfb5ecd75f99dc6133477696ddd1c |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 22115463 |
|---|