Nuclear trafficking in amyotrophic lateral sclerosis and frontotemporal lobar degeneration
| Autor: | Ana Bajc Česnik, Sonja Prpar Mihevc, Simona Darovic, Anja Kovanda, Vera Župunski, Boris Rogelj |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Active Transport Cell Nucleus Biology TARDBP 03 medical and health sciences 0302 clinical medicine C9orf72 medicine Humans Amyotrophic lateral sclerosis Cell Nucleus C9orf72 Protein Amyotrophic Lateral Sclerosis Proteins Frontotemporal lobar degeneration medicine.disease DNA-Binding Proteins 030104 developmental biology Nucleocytoplasmic Transport RNA-Binding Protein FUS Neurology (clinical) Frontotemporal Lobar Degeneration Trinucleotide repeat expansion Neuroscience 030217 neurology & neurosurgery Frontotemporal dementia |
| Zdroj: | Brain : a journal of neurology. 140(1) |
| ISSN: | 1460-2156 |
| Popis: | Amyotrophic lateral sclerosis and frontotemporal lobar degeneration are two ends of a phenotypic spectrum of disabling, relentlessly progressive and ultimately fatal diseases. A key characteristic of both conditions is the presence of TDP-43 (encoded by TARDBP) or FUS immunoreactive cytoplasmic inclusions in neuronal and glial cells. This cytoplasmic mislocalization of otherwise predominantly nuclear RNA binding proteins implies a perturbation of the nucleocytoplasmic shuttling as a possible event in the pathogenesis. Compromised nucleocytoplasmic shuttling has recently also been associated with a hexanucleotide repeat expansion mutation in C9orf72, which is the most common genetic cause of amyotrophic lateral sclerosis and frontotemporal lobar degeneration, and leads to accumulation of cytoplasmic TDP-43 inclusions. Mutation in C9orf72 may disrupt nucleocytoplasmic shuttling on the level of C9ORF72 protein, the transcribed hexanucleotide repeat RNA, and/or dipeptide repeat proteins translated form the hexanucleotide repeat RNA. These defects of nucleocytoplasmic shuttling may therefore, constitute the common ground of the underlying disease mechanisms in different molecular subtypes of amyotrophic lateral sclerosis and frontotemporal lobar degeneration. |
| Databáze: | OpenAIRE |
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