TDP-43 and Inflammation: Implications for Amyotrophic Lateral Sclerosis and Frontotemporal Dementia
Year: 2021
Type: review
Abstract: 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.
DOI: 10.3390/ijms22157781
Institution: Macquarie University
Language: English
Subfield: Clinical Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,160
Awards: G1056987646, Site-specific Tau Phosphorylation to Treat and Understand Alzheimer’s Disease, G1525095782, G3369440641, Novel pathomechanisms and treatment approaches in Alzheimer’s disease and related forms of dementia, Frontotemporal dementia and motor neurodegenerative syndromes, Targeting pathogenic TAR DNA-binding protein 43 to treat frontotemporal dementia and motor neuron disease, Novel pathomechanisms and therapeutic targets in neurodegenerative diseases, The Role of LIM Domain Kinase 1 in the Pathogenesis of Alzheimer’s Disease
OpenAlex ID: W3183448209