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Multi-phaseted problems of TDP-43 in selective neuronal vulnerability in ALS
- Source :
- Cellular and Molecular Life Sciences
- Publication Year :
- 2021
- Publisher :
- Springer Science and Business Media LLC, 2021.
-
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.
- Subjects :
- 0301 basic medicine
Heterogeneous nuclear ribonucleoprotein
Review
Biology
TARDBP
03 medical and health sciences
Cellular and Molecular Neuroscience
0302 clinical medicine
mental disorders
medicine
Animals
Humans
Coding region
Motor Neuron Disease
Amyotrophic lateral sclerosis
Molecular Biology
Pharmacology
Amyotrophic Lateral Sclerosis
nutritional and metabolic diseases
Cell Biology
Motor neuron
medicine.disease
nervous system diseases
DNA-Binding Proteins
030104 developmental biology
medicine.anatomical_structure
Cytoplasm
Molecular Medicine
Neuroscience
030217 neurology & neurosurgery
Intracellular
Function (biology)
Subjects
Details
- ISSN :
- 14209071 and 1420682X
- Volume :
- 78
- Database :
- OpenAIRE
- Journal :
- Cellular and Molecular Life Sciences
- Accession number :
- edsair.doi.dedup.....c41442da3a5f9b53afe389530542222e