دورية أكاديمية
Frontotemporal dementia-like disease progression elicited by seeded aggregation and spread of FUS.
| العنوان: | Frontotemporal dementia-like disease progression elicited by seeded aggregation and spread of FUS. |
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| المؤلفون: | Vazquez-Sanchez, Sonia, Tilkin, Britt, Gasset-Rosa, Fatima, Zhang, Sitao, Piol, Diana, McAlonis-Downes, Melissa, Artates, Jonathan, Govea-Perez, Noe, Verresen, Yana, Guo, Lin, Cleveland, Don W, Shorter, James, Da Cruz, Sandrine |
| المصدر: | Mol Neurodegener ; ISSN:1750-1326 ; Volume:19 ; Issue:1 |
| بيانات النشر: | BioMed Central |
| سنة النشر: | 2024 |
| المجموعة: | PubMed Central (PMC) |
| مصطلحات موضوعية: | Aggregation, Amyotrophic lateral sclerosis (ALS), FUS-proteinopathy, Frontotemporal lobar degeneration (FTLD), Spreading |
| الوصف: | RNA binding proteins have emerged as central players in the mechanisms of many neurodegenerative diseases. In particular, a proteinopathy of fused in sarcoma (FUS) is present in some instances of familial Amyotrophic lateral sclerosis (ALS) and about 10% of sporadic Frontotemporal lobar degeneration (FTLD). Here we establish that focal injection of sonicated human FUS fibrils into brains of mice in which ALS-linked mutant or wild-type human FUS replaces endogenous mouse FUS is sufficient to induce focal cytoplasmic mislocalization and aggregation of mutant and wild-type FUS which with time spreads to distal regions of the brain. Human FUS fibril-induced FUS aggregation in the mouse brain of humanized FUS mice is accelerated by an ALS-causing FUS mutant relative to wild-type human FUS. Injection of sonicated human FUS fibrils does not induce FUS aggregation and subsequent spreading after injection into naïve mouse brains containing only mouse FUS, indicating a species barrier to human FUS aggregation and its prion-like spread. Fibril-induced human FUS aggregates recapitulate pathological features of FTLD including increased detergent insolubility of FUS and TAF15 and amyloid-like, cytoplasmic deposits of FUS that accumulate ubiquitin and p62, but not TDP-43. Finally, injection of sonicated FUS fibrils is shown to exacerbate age-dependent cognitive and behavioral deficits from mutant human FUS expression. Thus, focal seeded aggregation of FUS and further propagation through prion-like spread elicits FUS-proteinopathy and FTLD-like disease progression. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| العلاقة: | https://doi.org/10.1186/s13024-024-00737-5Test; https://pubmed.ncbi.nlm.nih.gov/38862967Test; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11165889Test/ |
| DOI: | 10.1186/s13024-024-00737-5 |
| الإتاحة: | https://doi.org/10.1186/s13024-024-00737-5Test https://pubmed.ncbi.nlm.nih.gov/38862967Test https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11165889Test/ |
| حقوق: | © 2024. The Author(s). |
| رقم الانضمام: | edsbas.F284926C |
| قاعدة البيانات: | BASE |
| DOI: | 10.1186/s13024-024-00737-5 |
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