Tolperisone hydrochloride improves motor functions in Parkinson's disease via MMP-9 inhibition and by downregulating p38 MAPK and ERK1/2 signaling cascade

This study explores the modulation of MMP-9 expression via the MAPK/ERK signaling cascade and its potential therapeutic implications in the context of PD-associated motor dysfunction. Here, tolperisone hydrochloride (TL), a muscle relaxant that blocks voltage-gated sodium and calcium channels, was used as a treatment to observe its effect on MAPK signaling and MMP-9 expression. Rotenone (RT) exposure in mice resulted in a significant reduction in substantia nigra and primary motor cortex neurons, which were further evidenced by impairments in motor function. When TL was administered, neuron count was restored (89.0 ± 4.78 vs 117.0 ± 4.46/mm2), and most of the motor dysfunction was alleviated. Mechanistically, TL reduced the protein expression of phospho-p38MAPK (1.06 fold vs 1.00 fold) and phospho-ERK1/2 (1.16 fold vs 1.02 fold), leading to the inhibition of MAPK signaling, as well as reduced MMP-9 concentrations (2.76 ± 0.10 vs 1.94 ± 0.10 ng/mL) in the process of rescuing RT-induced neuronal cell death and motor dysfunction. Computational analysis further revealed TL's potential inhibitory properties against MMP-9 along with N and L-type calcium channels. These findings shed light on TL's neuroprotective effects via MMP-9 inhibition and MAPK signaling downregulation, offering potential therapeutic avenues for PD-associated motor dysfunction.PMID:38513594 | DOI:10.1016/j.biopha.2024.116438

Source: Biomedicine and pharmacotherapy = Biomedecine and pharmacotherapie - March 21, 2024 Category: Drugs & Pharmacology Authors: Bushra Zaman Irona Mostafa Tazree Hassan Shamim Ahmed Nusrat Jahan Ikbal Esha Fowzia Afsana Chowdhury Tory Bosu Humayra Noor Chowdhury Anup Mallick Mm Shanjid Islam Ayesha Sharmin Kabir M Uddin Md Mainul Hossain Mahbubur Rahman Source Type: research