التفاصيل البيبلوغرافية
| العنوان: |
Muscle microRNA signatures as biomarkers of disease progression in amyotrophic lateral sclerosis |
| المؤلفون: |
Ying Si, Xianqin Cui, David K. Crossman, Jiaying Hao, Mohamed Kazamel, Yuri Kwon, Peter H. King |
| المصدر: |
Neurobiology of Disease, Vol 114, Iss , Pp 85-94 (2018) |
| بيانات النشر: |
Elsevier, 2018. |
| سنة النشر: |
2018 |
| المجموعة: |
LCC:Neurosciences. Biological psychiatry. Neuropsychiatry |
| مصطلحات موضوعية: |
Myomirs, miRNA sequencing, G93A SOD1 mouse, Human ALS muscle biopsies, Ingenuity pathway analysis, Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571 |
| الوصف: |
ALS is a fatal neurodegenerative disorder of motor neurons leading to progressive atrophy and weakness of muscles. Some of the earliest pathophysiological changes occur at the level of skeletal muscle and the neuromuscular junction. We previously identified distinct mRNA patterns, including members of the Smad and TGF-β family, that emerge in muscle tissue at the earliest (pre-clinical) stages. These patterns track disease progression in the mutant SOD1 mouse and are present in human ALS muscle. Because miRNAs play a direct regulatory role in mRNA expression, we hypothesized in this study that there would be distinct miRNA patterns in ALS muscle appearing in early stages that could track disease progression. We performed next-generation miRNA sequencing on muscle samples from G93A SOD1 mice at early (pre-clinical) and late (symptomatic) stages, and identified distinct miRNA patterns at both stages with some overlap. An Ingenuity Pathway Analysis predicted effects on a number of pathways relevant to ALS including TGF-β signaling, axon guidance signaling, and mitochondrial function. A subset of miRNAs was validated in the G93A SOD1 mouse at four stages of disease, and several appeared to track disease progression, including miR-206. We assessed these miRNAs in a large cohort of human ALS and disease control samples and found that some had similar changes but were not specific for ALS. Surprisingly, miR-206 levels did not change overall compared to normal controls, but did correlate with changes in strength of the muscle biopsied. In summary, we identified distinct miRNA patterns in ALS muscle that reflected disease stage which could potentially be used as biomarkers of disease activity. |
| نوع الوثيقة: |
article |
| وصف الملف: |
electronic resource |
| اللغة: |
English |
| تدمد: |
1095-953X |
| Relation: |
http://www.sciencedirect.com/science/article/pii/S096999611830041X; https://doaj.org/toc/1095-953X |
| DOI: |
10.1016/j.nbd.2018.02.009 |
| URL الوصول: |
https://doaj.org/article/2d9018d9ab03460daa8f22edd630b1f4 |
| رقم الانضمام: |
edsdoj.2d9018d9ab03460daa8f22edd630b1f4 |
| قاعدة البيانات: |
Directory of Open Access Journals |