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Aging and disease
Feb 01, 2024;16 (2): 693-713.

Drug Screening and Validation Targeting TDP-43 Proteinopathy for Amyotrophic Lateral Sclerosis.

Jiaqi Xin, Sen Huang, Jing Wen, Yunhao Li, Ang Li, Senthil Kumaran Satyanarayanan, Xiaoli Yao, Huanxing Su
Author Information
  1. Jiaqi Xin: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China.
  2. Sen Huang: Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University; Guangdong Provincial Key Laboratory of Diagnosis and Treatment of Major Neurological Diseases; National Key Clinical Department and Key Discipline of Neurology, Guangzhou, China.
  3. Jing Wen: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China.
  4. Yunhao Li: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China.
  5. Ang Li: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China.
  6. Senthil Kumaran Satyanarayanan: Centre for Regenerative Medicine and Health, Hong Kong Institute of Science & Innovation, Chinese Academy of Sciences, Hong Kong Science Park, Hong Kong, China.
  7. Xiaoli Yao: Department of Neurology, The First Affiliated Hospital, Sun Yat-sen University; Guangdong Provincial Key Laboratory of Diagnosis and Treatment of Major Neurological Diseases; National Key Clinical Department and Key Discipline of Neurology, Guangzhou, China.
  8. Huanxing Su: State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macao, China.
PMID: 38739934 DOI: 10.14336/AD.2024.0440

Abstract

Amyotrophic lateral sclerosis (ALS) stands as a rare, yet severely debilitating disorder marked by the deterioration of motor neurons (MNs) within the brain and spinal cord, which is accompanied by degenerated corticobulbar/corticospinal tracts and denervation in skeletal muscles. Despite ongoing research efforts, ALS remains incurable, attributed to its intricate pathogenic mechanisms. A notable feature in the pathology of ALS is the prevalence of TAR DNA-binding protein 43 (TDP-43) proteinopathy, detected in approximately 97% of ALS cases, underscoring its significance in the disease's progression. As a result, strategies targeting the aberrant TDP-43 protein have garnered attention as a potential avenue for ALS therapy. This review delves into the existing drug screening systems aimed at TDP-43 proteinopathy and the models employed for drug efficacy validation. It also explores the hurdles encountered in the quest to develop potent medications against TDP-43 proteinopathy, offering insights into the intricacies of drug discovery and development for ALS. Through this comprehensive analysis, the review sheds light on the critical aspects of identifying and advancing therapeutic solutions for ALS.

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MeSH Term

Amyotrophic Lateral Sclerosis
Humans
TDP-43 Proteinopathies
Drug Evaluation, Preclinical
DNA-Binding Proteins
Animals

Chemicals

TARDBP protein, human
DNA-Binding Proteins
Journal Article Review
Article has an altmetric score of 7

Word Cloud

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