Synthesis and evaluation of peptidic metal chelators for neuroprotection in neurodegenerative diseases.
J Pept Res
; 66(4): 190-203, 2005 Oct.
Article
en En
| MEDLINE
| ID: mdl-16138857
ABSTRACT
A series of novel derivatives of neuropeptides with a metal-chelating moiety was synthesized and examined for various properties related to iron (Fe) chelation and neuroprotective action. All derivatives chelated Fe to form stable Fe complexes in water. Some strongly inhibited Fe-induced lipid peroxidation with an IC(50) value of about 12 microm. In PC12 cell culture, several compounds, at concentrations as low as 1 microm, attenuated serum-free stimulated cell death and improved cell survival by 20-35%. At this concentration, these analogs also protected against 6-hydroxydopamine (6-OHDA)-induced cell death, increasing cell viability by 20-30%. Electron paramagnetic resonance (EPR) studies indicated that besides being good Fe chelators, these analogs act as radical scavengers to directly scavenge hydroxyl radicals. Together, the data indicate that some of the analogs could be further developed as possible neuroprotective agents for treatment of neurodegenerative diseases such as Parkinson's, Alzheimer's, and Huntington's diseases, Friedreich's atxia, amyotrophic, and lateral sclerosis where Fe misregulation has been reported.
Buscar en Google
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Neuropéptidos
/
Quelantes
/
Enfermedades Neurodegenerativas
Límite:
Animals
Idioma:
En
Revista:
J Pept Res
Asunto de la revista:
BIOQUIMICA
Año:
2005
Tipo del documento:
Article
País de afiliación:
Israel