TDP-43 regulation of stress granule dynamics in neurodegenerative disease-relevant cell types
Autor: | Alexandre Prat, Yousra Khalfallah, Camille Grasmuck, Rachel Kuta, Christine Vande Velde, Heather D. Durham |
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Jazyk: | angličtina |
Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Cell type Aging Cell Down-Regulation lcsh:Medicine Degeneration (medical) Disease Biology Cytoplasmic Granules Article 03 medical and health sciences Mice Stress granule Stress Physiological mental disorders medicine Animals Humans lcsh:Science Cells Cultured Cerebral Cortex Motor Neurons Multidisciplinary Dynamics (mechanics) Amyotrophic Lateral Sclerosis lcsh:R Cortical neurons Fibroblasts In vitro DNA-Binding Proteins Oxidative Stress 030104 developmental biology medicine.anatomical_structure Astrocytes Frontotemporal Dementia lcsh:Q Neuroscience |
Zdroj: | Scientific Reports, Vol 8, Iss 1, Pp 1-13 (2018) Scientific Reports |
ISSN: | 2045-2322 |
Popis: | Stress granules (SGs) are cytoplasmic foci that form in response to various external stimuli and are essential to cell survival following stress. SGs are studied in several diseases, including ALS and FTD, which involve the degeneration of motor and cortical neurons, respectively, and are now realized to be linked pathogenically by TDP-43, originally discovered as a component of ubiquitin-positive aggregates within patients’ neurons and some glial cells. So far, studies to undercover the role of TDP-43 in SGs have used primarily transformed cell lines, and thus rely on the extrapolation of the mechanisms to cell types affected in ALS/FTD, potentially masking cell specific effects. Here, we investigate SG dynamics in primary motor and cortical neurons as well as astrocytes. Our data suggest a cell and stress specificity and demonstrate a requirement for TDP-43 for efficient SG dynamics. In addition, based on our in vitro approach, our data suggest that aging may be an important modifier of SG dynamics which could have relevance to the initiation and/or progression of age-related neurodegenerative diseases. |
Databáze: | OpenAIRE |
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