1. Academic Validation
  2. Prevention of Huntington's Disease-Like Behavioral Deficits in R6/1 Mouse by Tolfenamic Acid Is Associated with Decreases in Mutant Huntingtin and Oxidative Stress

Prevention of Huntington's Disease-Like Behavioral Deficits in R6/1 Mouse by Tolfenamic Acid Is Associated with Decreases in Mutant Huntingtin and Oxidative Stress

  • Oxid Med Cell Longev. 2019 Mar 26;2019:4032428. doi: 10.1155/2019/4032428.
Peng Liu 1 Yinjie Li 1 Wei Yang 1 Danyang Liu 1 Xuefei Ji 1 Tianyan Chi 1 Zhutao Guo 2 Lin Li 3 Libo Zou 1
Affiliations

Affiliations

  • 1 Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang 110016, China.
  • 2 Department of Clinical Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
  • 3 Key Laboratory of Neurodegenerative Diseases (Capital Medical University), Ministry of Education, Beijing 100053, China.
Abstract

Tolfenamic acid is a nonsteroidal anti-inflammatory drug with neuroprotective properties, and it alleviates learning and memory deficits in the APP transgenic mouse model of Alzheimer's disease. However, whether tolfenamic acid can prevent motor and memory dysfunction in transgenic animal models of Huntington's disease (HD) remains unclear. To this end, tolfenamic acid was orally administered to transgenic R6/1 mice from 10 to 20 weeks of age, followed by several behavioral tests to evaluate motor and memory function. Tolfenamic acid improved motor coordination in R6/1 mice as tested by rotarod, grip strength, and locomotor behavior tests and attenuated memory dysfunction as analyzed using the novel object recognition test and passive avoidance test. Tolfenamic acid decreased the expression of mutant Huntingtin in the striatum of 20-week-old R6/1 mice by inhibiting specificity protein 1 expression and enhancing autophagic function. Furthermore, tolfenamic acid exhibited antioxidant effects in both R6/1 mice and PC12 cell models. Collectively, these results suggest that tolfenamic acid has a good therapeutic effect on R6/1 mice, and may be a potentially useful agent in the treatment of HD.

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