TDP-43 and neurodegenerative diseases

Manoj Kumar Jaiswal

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review

Abstract

Over the years the transactive response DNA-binding protein (TDP-43), a highly conserved 43kDa nuclear protein, has been acknowledged as a vital protein in brain health and neuropathological disorders such as amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), Alzheimer's disease (AD), Lewy body dementia (LBD), and Parkinson disease (PD). Description of TDP-43 dates back to 1892 when neurologist Arnold Pick first described progressive dementia characterized by atrophy that diverged both clinically and pathophysiologically from AD. In 2006, TDP-43 was identified in ALS and FTD recognized by cytoplasmic inclusions that label ubiquitin (+), whereas tau and α-synuclein stains were negative. Since then, several discoveries have been made which have led to a better understanding of the pathophysiological function of TDP-43 and its intricate links to ALS, FTD, AD, PD, dementia, and few other neurological diseases, all of which shared some common disease mechanisms. In this book chapter, we précis past findings, up-to-date evidence of common physiological function of TDP-43 and the TDP-43 pathobiology witnessed in FTD-TDP, ALS-TDP, and other neurodegenerative diseases such as AD, PD, and LBD. In addition, we deliberate on the accumulating data indicating FTD-TDP and ALS-TDP as two ends of a disease spectrum characterized by a fundamental, main TDP-43 proteinopathy and, thus, contemplate on its implication in precision medicine. Finally, we discuss the status of new advances in TDP-43-associated discovery to neurological practice and care, including the novel prospects to develop better precision diagnostics kits and disease-modifying therapies for ALS-TDP, FTD-TDP, AD, LBD, PD, and other related neurological disorders showing characteristic TDP-43 pathological symptoms.

Original languageEnglish
Title of host publicationTDP-43 and Neurodegeneration
Subtitle of host publicationFrom Bench to Bedside
PublisherElsevier
Pages1-26
Number of pages26
ISBN (Electronic)9780128200667
ISBN (Print)9780128204405
DOIs
StatePublished - 1 Jan 2022

Keywords

  • Alzheimer's disease (AD)
  • Amyotrophic lateral sclerosis (ALS)
  • Frontotemporal dementia (FTD)
  • Lewy body dementia (LBD)
  • Parkinson disease (PD)
  • TARDBP
  • Transactive response DNA-Binding protein 43 (TDP-43)

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