Moderate modulation of disease in the G93A model of ALS by the compound 2-(2-hydroxyphenyl)-benzoxazole (HBX)

Teresa M. Evans, Arunabh Bhattacharya, Yun Shi, Wenbo Qi, Travis J. Block, Asish Chaudhuri, Alakananda Ray Chaudhuri, Kara Hawker, Holly Van Remmen

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Amyotrophic lateral sclerosis (ALS) is a progressive and fatal neurological disease characterized by degeneration and death of motor neurons. Aberrant protein aggregation and oxidative stress are implicated in the etiology of ALS; thus preventing propagation of early aggregation events and oxidative damage could be an effective therapy. We tested the effect of dietary supplementation (initiated 40 days of age) with 2-(2-hydroxyphenyl)-benzoxazole (HBX), a compound with metal chelator and anti-aggregation properties, on disease onset, progression and lifespan in the G93A mouse model of ALS. Tests were not sufficiently powerful to detect any change to survival distribution of mice treated with HBX. However, the disease onset was delayed and max lifespan was increased in the treatment group. Additionally, disease progression was moderated as shown by reduced neuromuscular denervation measured by repetitive nerve stimulation. F2-isoprostanes, a marker of oxidative damage, are elevated in skeletal muscle from G93A mice at onset and this increase is prevented in HBX fed G93A mice. Furthermore, HBX treatment reduced mutant SOD1 protein aggregation in whole spinal cord of G93A mice at disease onset. Overall, our data suggests that HBX may be able to improve the degenerative symptoms of ALS through the prevention of oxidative damage and protein aggregation. Further studies are needed to uncover the mechanistic effects of HBX in ameliorating ALS pathology.

Original languageEnglish (US)
Pages (from-to)1-7
Number of pages7
JournalNeuroscience Letters
Volume624
DOIs
StatePublished - Jun 15 2016

Keywords

  • Amyotrophic lateral sclerosis
  • Chelation
  • Denervation
  • Mouse model
  • Protein aggregation
  • Treatment

ASJC Scopus subject areas

  • Neuroscience(all)

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    Evans, T. M., Bhattacharya, A., Shi, Y., Qi, W., Block, T. J., Chaudhuri, A., Chaudhuri, A. R., Hawker, K., & Van Remmen, H. (2016). Moderate modulation of disease in the G93A model of ALS by the compound 2-(2-hydroxyphenyl)-benzoxazole (HBX). Neuroscience Letters, 624, 1-7. https://doi.org/10.1016/j.neulet.2016.04.035