| RRC ID |
64793
|
| 著者 |
Asakawa K, Handa H, Kawakami K.
|
| タイトル |
Multi-phaseted problems of TDP-43 in selective neuronal vulnerability in ALS.
|
| ジャーナル |
Cell Mol Life Sci
|
| Abstract |
Transactive response DNA-binding protein 43 kDa (TDP-43) encoded by the TARDBP gene is an evolutionarily conserved heterogeneous nuclear ribonucleoprotein (hnRNP) that regulates multiple steps of RNA metabolism, and its cytoplasmic aggregation characterizes degenerating motor neurons in amyotrophic lateral sclerosis (ALS). In most ALS cases, cytoplasmic TDP-43 aggregation occurs in the absence of mutations in the coding sequence of TARDBP. Thus, a major challenge in ALS research is to understand the nature of pathological changes occurring in wild-type TDP-43 and to explore upstream events in intracellular and extracellular milieu that promote the pathological transition of TDP-43. Despite the inherent obstacles to analyzing TDP-43 dynamics in in vivo motor neurons due to their anatomical complexity and inaccessibility, recent studies using cellular and animal models have provided important mechanistic insights into potential links between TDP-43 and motor neuron vulnerability in ALS. This review is intended to provide an overview of the current literature on the function and regulation of TDP-43-containing RNP granules or membraneless organelles, as revealed by various models, and to discuss the potential mechanisms by which TDP-43 can cause selective vulnerability of motor neurons in ALS.
|
| 公開日 |
2021-3-11
|
| DOI |
10.1007/s00018-021-03792-z
|
| PII |
10.1007/s00018-021-03792-z
|
| PMID |
33709256
|
| PMC |
PMC8195926
|
| MeSH |
Amyotrophic Lateral Sclerosis / complications*
Amyotrophic Lateral Sclerosis / metabolism
Amyotrophic Lateral Sclerosis / pathology
Animals
DNA-Binding Proteins / chemistry
DNA-Binding Proteins / metabolism*
Humans
Motor Neuron Disease / etiology
Motor Neuron Disease / metabolism
Motor Neuron Disease / pathology*
|
| IF |
6.496
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| リソース情報 |
| ゼブラフィッシュ |
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