TDP-43 and Neurodegeneration

From Bench to Bedside

1st Edition - October 23, 2021
Imprint: Academic Press
Editors: Vijay Kumar, Manoj Kumar Jaiswal
Language: English
Paperback ISBN:
9 7 8 - 0 - 1 2 - 8 2 0 0 6 6 - 7
eBook ISBN:
9 7 8 - 0 - 1 2 - 8 2 0 4 4 0 - 5

Aggregates of the TAR DNA binding protein 43 (TDP-43), are hallmark features of the neurodegenerative diseases Amyotrophic Lateral Sclerosis (ALS) and frontotemporal dementia (F… Read more

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Aggregates of the TAR DNA binding protein 43 (TDP-43), are hallmark features of the neurodegenerative diseases Amyotrophic Lateral Sclerosis (ALS) and frontotemporal dementia (FTD), with overlapping clinical, genetic and pathological features. TDP-43 and Neurodegeneration: From Bench to Bedside summarizes new findings in TDP-43 pathobiology and proteinopathies. The book summarizes TDP-43’s structure, function, biology, misfolding, aggregation, pathogenesis and therapeutics. It includes autophagy-mediated therapy, role of stress granule, novel genetic, cell culture-based models, systems biology for precision medicine, development of stem cells and mechanism-based therapies that can target ALS and other related neurodegenerative diseases. This book is written for neuroscientists, neurologists, clinicians, advanced graduate students, drug discovery researchers, as well as cellular and molecular biologists involved in ALS, motor neuron disease (MND) and other neurodegenerative disorders.

Cover image
Title page
Table of Contents
Copyright
List of contributors
Preface
Chapter 1. TDP-43 and neurodegenerative diseases: past, present, and future
Introduction
TDP-43 physiological and pathophysiological function
TDP-43 and mitochondria
TDP-43 and gene regulation
TDP-43 as a potential therapeutic biomarker
TDP-43 and novel therapy
TDP-43 and its relevance to clinical practice
Discussions and perspectives
List of abbreviations
Conflicts of interests
Author contributions
Chapter 2. Structural dissection of TDP-43: insights into physiological and pathological self-assembly
Introduction
Conclusion
Chapter 3. Posttranslational modifications of TDP-43
Introduction
Ubiquitination
Phosphorylation
C-terminal fragmentation
Cysteine oxidation
Acetylation
Conclusion
Abbreviations
Chapter 4. Regulation of autophagy by TDP-43: a promising therapeutic intervention in neurodegenerative diseases
Introduction
Autophagy
Autophagy in neurodegenerative disorders
RNA-binding proteins in autophagy
TDP-43 and autophagy in ALS
TDP-43 interactome
Therapeutic applications: targeting autophagy in the treatment of neurological disorders
Conclusion and future prospectives
Conflict of interest
Chapter 5. Prion-like behavior of TDP-43 aggregates and its implication to disease
Introduction
Aggregation and amyloidogenic conversion of TDP-43
Prion-like properties of TDP-43 aggregates
Intracellular aggregation and localization of TDP-43 prions
Intercellular transmission and infectivity of TDP-43 prions
Conclusion
Chapter 6. Search for functions of intrinsically disordered prion-like domains for FET proteins involved in amyotrophic lateral sclerosis and frontotemporal dementia
Introduction
Results and discussion
Materials and methods
Conclusions
Chapter 7. A systems biology approach to understand the role of TDP-43 in amyotrophic lateral sclerosis
Introduction
Results
Discussion and conclusion
Chapter 8. TDP-43 proteinopathy mechanisms from non-mammalian model systems
Introduction
The yeast Saccharomyces cerevisiae model of the TDP-43 proteinopathy
The Caenorhabditis elegans model of the TDP-43 proteinopathy
The Drosophila model of the TDP-43 proteinopathy
The zebrafish model of the TDP-43 proteinopathy
Conclusions and future directions
Chapter 9. New opportunities for treatment of neurodegenerative disease through the modulation of TDP-43
Introduction
TDP-43 proteinopathy
Standard-of-care medications in the treatment of ALS
Therapeutic modulation of TDP-43
Discussion and future directions
List of abbreviations
Conflicts of interests
Author contributions
Index

Vijay Kumar

Vijay Kumar, Ph.D. has been Assistant Professor in Amity University, since 2018. He obtained his PhD in Biophysics from All India Institute of Medical sciences, New Delhi, India and did his Postdoctoral training from the university of Massachusetts Medical school, Massachusetts, USA. His postdoctoral research was focused on folding and aggregation studies of proteins, SOD1 and TDP-43 involved in motor neuron disease, ALS and FTD. Back to India, he worked as a Principal Investigator under DST-SERB Young Scientist Scheme in Jamia Millia Islamia (A central university), New Delhi. His present research interests focus on the area of folding, misfolding and aggregation of proteins and the role of toxic RNA species involved in the Neurodegenerative Diseases. Dr. Kumar is a member of the Protein Society, Indian Biophysical Society (IBS), Indian Academy of Neurosciences (IAN), and the International society for Neurochemistry (ISN). He had a Junior Research Fellowship/Senior Research fellowship (SRF) from Council of Scientific and Industrial Research (CSIR), New Delhi, India and a DAAD Fellowship , Germany.

Affiliations and expertise

Assistant Professor, Amity Institute of Neuropsychology and Neurosciences, Amity University, Noida, India

Manoj Kumar Jaiswal

Manoj Kumar Jaiswal, Ph.D., has been non-tenure track faculty (Instructor) in the Department of Psychiatry at Icahn School of Medicine at Mount Sinai, NY, since 2017. He obtained PhD degree at the Georg-August University, Goettingen, Germany, and postdoctoral training at MIT, Cambridge, MA and CNRM, Bethesda, MD. More recently, Dr. Jaiswal is a Research Scientist in the Department of Psychiatry at the Columbia University Medical Center in NY. His current research focuses on studies related to neurodegeneration in ALS, motor neuron disease, brain Injury, and psychiatric disorders. He is a recipient of an NIH Career Development Award and was appointed as a Career Development Fellow and later a Senior Research Fellow at the CNRM in Bethesda, MD where he studied molecular mechanisms of Traumatic Brain Injury (TBI) using 2-photon in-vivo imaging and 3-D microscopy. Dr. Jaiswal, has received numerous honors and awards, including scholarships and poster awards, and was invited to present lectures and seminars. He is a member of Society for Neuroscience (SfN) and the National Neurotrauma Society (NNS). He has been the Principal Investigator of a National Institute of Health/DoD: Pilot Project entitled: “Balance between inhibition and excitation and the vascular trauma in sensory barrel cortex after TBI: in-vivo imaging approach”. He is a reviewer and editor for many journals, including Scientific Reports, Annals of Neurology and Frontiers in Cellular Neuroscience. He has authored numerous articles, book and book chapters on Amyotrophic Lateral Sclerosis (ALS), Motor Neuron Disease and Psychiatric Disorders.

Affiliations and expertise

Department of Psychiatry, Icahn School of Medicine at Mount Sina, New York, NY, USA

Life Sciences

Physical Sciences & Engineering

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