Work

L-NRB alleviates amyotrophic lateral sclerosis by regulating P11-Htr4 signaling pathway

Year: 2024

Type: article

Abstract: L-NRB is a compound formed as a ring cleavage product of butylphthalide and borneol in a molar ratio 1:2. This study aimed to explore the therapeutic effect of L-NRB on amyotrophic lateral sclerosis (ALS) and its possible mechanism. SOD1-G93A mice were used as an ALS model. Behavioral tests, histopathological staining, Nissl staining, immunohistochemistry, enzyme-linked immunosorbent assays, and Western blotting were used to analyze the therapeutic effect. The underlying mechanism of L-NRB in treating ALS was investigated using transcriptomic analyses. It was found that L-NRB alleviated motor dysfunction, pathological changes in the gastrocnemius muscle, and motor neuron injuries. The results indicated that L-NRB had a neuroprotective function associated with the inhibition of neuroinflammation. The anti-apoptotic effect of L-NRB was found to be related to the regulation of the P11-Htr4 signaling pathway. In summary, the results demonstrated the therapeutic effect of L-NRB on ALS and suggest a promising new therapeutic candidate for ALS. • This study reported a novel small molecule, L-NRB, may be a potential drug for the treatment of ALS. • L-NRB could alleviate motor neuron damage and pathological changes of gastrocnemius muscle in ALS mice model. • L-NRB could inhibit neuroinflammation and apoptosis in SOD1-G93A mice. • It was reported for the first time that L-NRB could regulate the P11-Htr4 signaling pathway. • L-NRB could inhibit cell apoptosis and ameliorate the progression of ALS.

Source: Biomedicine & Pharmacotherapy

DOI: 10.1016/j.biopha.2024.117588