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
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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