To view this document, you will need to have Adobe Flash Player 10 or above installed.click here to install .
Novel therapeutic approaches for the treatment of neurodegenerative disorders comprise drug candidates designed specifically to act on multiple central nervous system targets. We have recently synthesized multifunctional, nontoxic, brain-permeable iron-chelating drugs, M30 and HLA20, possessing the N -propargylamine neuroprotective moiety of rasagiline (Azilect) and the iron-chelating moiety of VK28. The present study demonstrates that M30 and HLA20 possess a wide range of pharmacological activities in mouse NSC-34 motor neuron cells, including neuroprotective effects against hydrogen peroxide- and 3-morpholinosydnonimine-induced neurotoxicity, induction of differentiation, and up-regulation of hypoxia-inducible factor (HIF)-1 and HIF-target genes (enolase1 and vascular endothelial growth factor). Both compounds induced NSC-34 neuritogenesis, accompanied by a marked increase in the expression of brain-derived neurotrophic factor and growth-associated protein-43, which was inhibited by PD98059 and GF109203X, indicating the involvement of mitogen-activated protein kinase and protein kinase C pathways. A major finding was the ability of M30 to significantly extend the survival of G93A-SOD1 amyotrophic lateral sclerosis mice and delay the onset of the disease. These properties of the novel multimodal iron-chelating drugs possessing neuroprotective/neuritogenic activities may offer future therapeutic possibilities for motor neurodegenerative diseases.—Kupershmidt, L., Weinreb, O., Amit, T., Mandel, S., Carri, M. T., Youdim, M. B. H. Neuroprotective and neuritogenic activities of novel multimodal iron-chelating drugs in motor-neuron-like NSC-34 cells and transgenic mouse model of amyotrophic lateral sclerosis.
To view this document, you will need to have Adobe Flash Player 10 or above installed.click here to install .
This is a preview. The total pages displayed will be limited.
Rent for $0.99 FREE
Login
It seems like you have an account, please login to rent this article
Don't have an account yet? Sign up now!
To view the full-text of this article, sign up for a free DeepDyve account below.
A free Basic account also comes with 3 free rentals to help get you started.
It seems like you have an account, please login to rent this article
Just 30 seconds to go! Please check your inbox for a confirmation email to activate your account, then start using your 3 FREE rentals.
Learn more Existing user? Login here
Share this article:
facebook
twitter
Article Details
More Like This Article View All
dataSource[]=aspet&dataSource[]=aacc&dataSource[]=aacr&dataSource[]=aip&dataSource[]=ajnr&dataSource[]=appi_book&dataSource[]=appi_journal&dataSource[]=asip&dataSource[]=asm&dataSource[]=asn&dataSource[]=aspb&dataSource[]=annual_reviews&dataSource[]=arxiv&dataSource[]=acm&dataSource[]=clinical_trials&dataSource[]=dailymed&dataSource[]=degruyter&dataSource[]=elsevier&dataSource[]=emerald&dataSource[]=emea&dataSource[]=epo&dataSource[]=faseb&dataSource[]=gsa&dataSource[]=health_affairs&dataSource[]=hindawi&dataSource[]=imedpub&dataSource[]=iucr&dataSource[]=iospress&dataSource[]=jbjs&dataSource[]=mesharpe&dataSource[]=mary_ann_liebert&dataSource[]=medline&dataSource[]=mit_press&dataSource[]=oxford&dataSource[]=pnas&dataSource[]=psyc_articles&dataSource[]=psyc_books&dataSource[]=psyc_critiques&dataSource[]=plos_journal&dataSource[]=pubmed_central&dataSource[]=rsna&dataSource[]=rockefeller&dataSource[]=sage&dataSource[]=spie&dataSource[]=springer&dataSource[]=taylor_francis&dataSource[]=aps&dataSource[]=the_scientist&dataSource[]=uc_press&dataSource[]=uspto_abstract&dataSource[]=pct
