Neuroprotection by the multitarget iron chelator M30 on age-related alterations in mice.
Mech Ageing Dev
; 133(5): 267-74, 2012 May.
Article
em En
| MEDLINE
| ID: mdl-22426424
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 ß-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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Envelhecimento
/
Quelantes
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Fármacos Neuroprotetores
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Hidroxiquinolinas
Limite:
Animals
Idioma:
En
Revista:
Mech Ageing Dev
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Israel
País de publicação:
Irlanda