Post-treatment with Meloxicam Attenuates MPP⁺-Induced Neurotoxicity via PI3K/Akt-Dependent Maintenance of Mcl-1
Abstract
Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the nigrostriatal pathway. Current treatments for PD primarily provide symptomatic relief through dopamine replacement; however, no neuroprotective drugs are currently clinically available. Our previous work demonstrated that meloxicam (MLX) protects against 1-methyl-4-phenylpyridinium (MPP+)-induced neurotoxicity in human neuroblastoma SH-SY5Y cells via the phosphatidylinositol 3-kinase (PI3K)/Akt pathway, independent of cyclooxygenase inhibition. However, the downstream mechanisms remain unclear. In this study, we examined which anti-apoptotic B-cell lymphoma-2 (Bcl-2) family proteins, including Bcl-2, Bcl-xL, and myeloid cell leukemia 1 (Mcl-1), contribute to MLX-mediated neuroprotection. We also evaluated whether post-treatment with MLX can rescue MPP+-induced neurotoxicity, considering its potential clinical applicability. Cell viability assays and Western blotting were performed to assess neuronal survival and protein expression. Our results show that post-treatment with MLX restored neuronal viability after MPP+ exposure through the PI3K/Akt/Mcl-1 pathway, indicating that MLX can attenuate MPP+-induced apoptotic progression even when administered at delayed time points. These findings elucidate the molecular basis of MLX-mediated neuroprotection and support the potential therapeutic repurposing of MLX as a neuroprotective agent for PD.
Related
- Antioxidant response and neurotransmitter modulation driven by oleuropein/alpha-lipoic acid attenuates lead-induced reproductive toxicity and neurotoxicity in Drosophila melanogaster
- Neurotoxicity associated with ALK inhibitors in the treatment of non-small cell lung cancer: an analysis of the FAERS database
- Hydrogen sulfide attenuates post-myocardial infarction cardiac fibrosis by modulating SENP1-dependent TEAD1 SUMOylation
- Oral Esketamine Maintenance Treatment for Treatment‐Resistant Depression: Clinical Outcomes During an Off‐Label Treatment Program
- Wastewater treatment attenuates ecological and human health resistome risk
BibTeX
@article{matsuura2026posttreatment,
title = {{Post-treatment with Meloxicam Attenuates MPP⁺-Induced Neurotoxicity via PI3K/Akt-Dependent Maintenance of Mcl-1}},
author = {Yasuhiro Matsuura and Takayuki Manabe and Tomoko Ohkubo and Masaya Kanda and Kuninori Iwayama and Naoya Kamiyama and Masayuki Chuma and Yoshikazu Tasaki},
journal = {Biological and Pharmaceutical Bulletin},
year = {2026},
month = oct,
doi = {10.1248/bpb.b26-00348},
url = {https://www.jstage.jst.go.jp/article/bpb/49/10/49_b26-00348/_article},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Post-treatment with Meloxicam Attenuates MPP⁺-Induced Neurotoxicity via PI3K/Akt-Dependent Maintenance of Mcl-1
AU - Yasuhiro Matsuura
AU - Takayuki Manabe
AU - Tomoko Ohkubo
AU - Masaya Kanda
AU - Kuninori Iwayama
AU - Naoya Kamiyama
AU - Masayuki Chuma
AU - Yoshikazu Tasaki
PY - 2026
DA - 2026/10/23
JO - Biological and Pharmaceutical Bulletin
DO - 10.1248/bpb.b26-00348
UR - https://www.jstage.jst.go.jp/article/bpb/49/10/49_b26-00348/_article
AB - Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the nigrostriatal pathway. Current treatments for PD primarily provide symptomatic relief through dopamine replacement; however, no neuroprotective drugs are currently clinically available. Our previous work demonstrated that meloxicam (MLX) protects against 1-methyl-4-phenylpyridinium (MPP+)-induced neurotoxicity in human neuroblastoma SH-SY5Y cells via the phosphatidylinositol 3-kinase (PI3K)/Akt pathway, independent of cyclooxygenase inhibition. However, the downstream mechanisms remain unclear. In this study, we examined which anti-apoptotic B-cell lymphoma-2 (Bcl-2) family proteins, including Bcl-2, Bcl-xL, and myeloid cell leukemia 1 (Mcl-1), contribute to MLX-mediated neuroprotection. We also evaluated whether post-treatment with MLX can rescue MPP+-induced neurotoxicity, considering its potential clinical applicability. Cell viability assays and Western blotting were performed to assess neuronal survival and protein expression. Our results show that post-treatment with MLX restored neuronal viability after MPP+ exposure through the PI3K/Akt/Mcl-1 pathway, indicating that MLX can attenuate MPP+-induced apoptotic progression even when administered at delayed time points. These findings elucidate the molecular basis of MLX-mediated neuroprotection and support the potential therapeutic repurposing of MLX as a neuroprotective agent for PD.
SN - 1347-5215
SN - 0918-6158
ER -