TDP-43 and Inflammation: Implications for Amyotrophic Lateral Sclerosis and Frontotemporal Dementia
Autor: | Yazi D. Ke, Lars M. Ittner, Fiona Bright, Annika van Hummel, Gabriella Chan |
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Rok vydání: | 2021 |
Předmět: |
0301 basic medicine
TDP-43 Review neuroinflammation Pathogenesis 0302 clinical medicine Ubiquitin Biology (General) Amyotrophic lateral sclerosis Spectroscopy biology Neurodegeneration neurodegeneration FTD General Medicine Computer Science Applications DNA-Binding Proteins Chemistry medicine.anatomical_structure Frontotemporal Dementia medicine.symptom Frontotemporal dementia QH301-705.5 Central nervous system Inflammation Catalysis Inorganic Chemistry 03 medical and health sciences mental disorders medicine Animals Humans Physical and Theoretical Chemistry QD1-999 Molecular Biology Neuroinflammation business.industry Amyotrophic Lateral Sclerosis Organic Chemistry nutritional and metabolic diseases medicine.disease immunity nervous system diseases 030104 developmental biology Mutation biology.protein ALS business Neuroscience 030217 neurology & neurosurgery |
Zdroj: | International Journal of Molecular Sciences, Vol 22, Iss 7781, p 7781 (2021) International Journal of Molecular Sciences |
ISSN: | 1422-0067 |
Popis: | The abnormal mislocalisation and ubiquitinated protein aggregation of the TAR DNA binding protein 43 (TDP-43) within the cytoplasm of neurons and glia in the central nervous system (CNS) is a pathological hallmark of early-onset neurodegenerative disorders amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The pathomechanisms underlying abnormal mislocalisation and aggregation of TDP-43 remain unknown. However, there is a growing body of evidence implicating neuroinflammation and immune-mediated mechanisms in the pathogenesis of neurodegeneration. Importantly, most of the evidence for an active role of immunity and inflammation in the pathogenesis of ALS and FTD relates specifically to TDP-43, posing the question as to whether immune-mediated mechanisms could hold the key to understanding TDP-43’s underlying role in neurodegeneration in both diseases. Therefore, this review aims to piece together key lines of evidence for the specific association of TDP-43 with key immune and inflammatory pathways to explore the nature of this relationship and the implications for potential pathomechanisms underlying neurodegeneration in ALS and FTD. |
Databáze: | OpenAIRE |
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