Related Experiment Video
Updated: May 24, 2026
Assessing Iron Deposition in the Brains of 5xFAD Mice by Perls'/DAB Staining
Published on: May 23, 2025
Neuroprotection by the multitarget iron chelator M30 on age-related alterations in mice
Lana Kupershmidt1, Tamar Amit, Orit Bar-Am
1Eve Topf Centers of Excellence for Neurodegenerative Diseases Research and Department of Pharmacology, Rappaport Family Research Institute Technion-Faculty of Medicine, Haifa 31096, Israel.
Abstract:
Based on a multimodal drug design paradigm, we have synthesized a multifunctional non-toxic, brain permeable iron chelating compound, M30, possessing the neuroprotective N-propargyl moiety of the anti-Parkinsonian drug, monoamine oxidase (MAO)-B inhibitor, rasagiline and the antioxidant-iron chelator moiety of an 8-hydroxyquinoline derivative of the iron chelator, VK28. Here, we report that a chronic systemic treatment of aged mice with M30 (1 and 5mg/kg; 4 times weekly for 6 months), had a significant positive impact on neuropsychiatry functions and cognitive age-related impairment. M30 significantly reduced cerebral iron accumulation as demonstrated by Perl's staining, accompanied by a marked decrease in cerebral β-amyloid plaques. In addition, our results demonstrate that M30 caused a significant inhibition of both MAO-A and -B activities in the cerebellum of aged mice, compared with vehicle-treated aged control mice. In summary, the present study indicates that the novel MAO inhibitor/iron chelating drug, M30, acting against multiple brain targets could reverse age-associated memory impairment and provide a potential treatment against the progression of neurodegeneration in ageing.
Insights
A novel drug, M30, combines iron chelation and MAO inhibition to reverse age-related memory loss in mice. This multi-target approach shows promise for treating neurodegeneration and cognitive decline in aging.
Area of Science:
- Neuroscience
- Pharmacology
- Drug Design
Background:
- Aging is associated with cognitive decline and neurodegeneration.
- Iron accumulation and monoamine oxidase (MAO) activity are implicated in age-related brain dysfunction.
- Existing treatments often target single pathways, limiting efficacy.
Purpose of the Study:
- To synthesize and evaluate a novel multifunctional compound, M30, for treating age-related cognitive impairment.
- To assess M30's impact on brain iron levels, amyloid plaques, and MAO activity in aged mice.
Main Methods:
- M30 synthesized using a multimodal drug design paradigm, incorporating neuroprotective and iron-chelating moieties.
- Aged mice received chronic systemic treatment with M30 (1 and 5mg/kg) for 6 months.
- Neuropsychiatric functions, cognitive performance, cerebral iron, beta-amyloid plaques, and MAO-A/B activities were assessed.
Main Results:
- M30 treatment significantly improved neuropsychiatric functions and reversed cognitive impairment in aged mice.
- Reduced cerebral iron accumulation and decreased beta-amyloid plaque load were observed.
- Significant inhibition of both MAO-A and MAO-B activities in the cerebellum was demonstrated.
Conclusions:
- The novel compound M30, acting as an MAO inhibitor and iron chelator, effectively reverses age-associated memory impairment.
- M30's multimodal action against multiple brain targets offers a potential therapeutic strategy for neurodegeneration in aging.
More Related Videos
04:48Setup of Capillary Electrophoresis-Inductively Coupled Plasma Mass Spectrometry (CE-ICP-MS) for Quantification of Iron Redox Species (Fe(II), Fe(III))
Published on: May 4, 2020
08:17A Mouse Model of Orthopedic Surgery to Study Postoperative Cognitive Dysfunction and Tissue Regeneration
Published on: February 27, 2018