Mithramycin, an agent for developing new therapeutic drugs for neurodegenerative diseases
Nobuhiro Osada1, Yasuhiro Kosuge, Kumiko Ishige
1Laboratory of Pharmacology, School of Pharmacy, Nihon University, Japan.
Abstract:
Mithramycin A (MTM) has been shown to inhibit cancer growth by blocking the binding of Sp-family transcription factors to gene regulatory elements and is used for the treatment of leukemia and testicular cancer in the United States. In contrast, MTM has also been shown to exert neuroprotective effects in normal cells. An earlier study showed that MTM protected primary cortical neurons against oxidative stress-induced cell death. Recently, we demonstrated that MTM suppressed endoplasmic reticulum (ER) stress-induced neuronal death in organotypic hippocampal slice cultures and cultured hippocampal cells through attenuation of ER stress-associated signal proteins. We also found that MTM decreased neuronal death in area CA1 of the hippocampus after transient global ischemia/reperfusion in mice and restored the ischemia/reperfusion-induced impairment of long-term potentiation in this area. MTM has been shown to prolong the survival of Huntington's disease model mice and to attenuate dopaminergic neurotoxicity in mice after repeated administration of methamphetamine. In this review, we provide an up to date overview of neuroprotective effects of MTM and less toxic MTM analogs, MTM SK and MTM SDK, on some of the neurodegenerative diseases and discuss the promise of MTM as an agent for developing new therapeutic drugs for such diseases.
Insights
Mithramycin A (MTM) demonstrates significant neuroprotective effects against various neuronal damages. This review highlights MTM
Area of Science:
- Neuroscience
- Pharmacology
- Molecular Biology
Background:
- Mithramycin A (MTM) is an anticancer drug that inhibits Sp transcription factors.
- MTM exhibits neuroprotective properties in normal cells, contrasting its anti-cancer mechanism.
- Previous studies indicated MTM's protection against oxidative stress and endoplasmic reticulum (ER) stress in neurons.
Purpose of the Study:
- To review the neuroprotective effects of Mithramycin A (MTM) and its analogs.
- To discuss the potential of MTM in treating neurodegenerative diseases.
- To provide an updated overview of MTM's therapeutic promise.
Main Methods:
- Review of existing literature on MTM's neuroprotective actions.
- Analysis of studies investigating MTM's effects on neuronal cell death models.
- Examination of MTM's impact on ER stress and ischemia/reperfusion injury.
Main Results:
- MTM suppresses ER stress-induced neuronal death by attenuating associated signal proteins.
- MTM reduces neuronal death in the hippocampus following ischemia/reperfusion.
- MTM prolongs survival in Huntington's disease models and mitigates methamphetamine-induced dopaminergic neurotoxicity.
Conclusions:
- MTM and its less toxic analogs (MTM SK, MTM SDK) show promise for neuroprotection.
- MTM's demonstrated efficacy in various neurodegenerative models warrants further therapeutic development.
- MTM represents a potential therapeutic agent for neurodegenerative diseases.
More Related Videos
06:51Systemic Delivery of MicroRNA Using Recombinant Adeno-associated Virus Serotype 9 to Treat Neuromuscular Diseases in Rodents
Published on: August 10, 2018
11:44Cellular Membrane Affinity Chromatography Columns to Identify Specialized Plant Metabolites Interacting with Immobilized Tropomyosin Kinase Receptor B
Published on: January 19, 2022
Related Concept Videos
01:15Anthelminthic Agents
01:29Drugs Affecting Neurotransmitter Synthesis
01:22Alzheimer's Disease: Treatment
01:25Inhibitors of Bacterial Protein Synthesis
01:26Neurochemical Transmission: Sites of Drug Action
01:29Microorganisms in Medicine and Therapeutics