An orally active anti-apoptotic molecule (CGP 3466B) preserves mitochondria and enhances survival in an animal model of motoneuron disease.

Détails

ID Serval
serval:BIB_8ED2557B6D1E
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
An orally active anti-apoptotic molecule (CGP 3466B) preserves mitochondria and enhances survival in an animal model of motoneuron disease.
Périodique
British journal of pharmacology
Auteur(s)
Sagot Y., Toni N., Perrelet D., Lurot S., King B., Rixner H., Mattenberger L., Waldmeier P.C., Kato A.C.
ISSN
0007-1188
Statut éditorial
Publié
Date de publication
2000
Peer-reviewed
Oui
Volume
131
Numéro
4
Pages
721-728
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't Publication Status: ppublish
Résumé
Apoptosis and mitochondrial dysfunction are thought to be involved in the aetiology of neurodegenerative diseases. We have tested an orally active anti-apoptotic molecule (CGP 3466B) that binds to glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in an animal model with motoneuron degeneration, i.e. a mouse mutant with progressive motor neuronopathy (pmn). In pmn/pmn mice, CGP 3466B was administered orally (10 - 100 nmol kg(-1)) at the onset of the clinical symptoms (2 weeks after birth). CGP 3466B slowed disease progression as determined by a 57% increase in life-span, preservation of body weight and motor performance. This improvement was accompanied by a decreased loss of motoneurons and motoneuron fibres as well as an increase in retrograde transport. Electron microscopic analysis showed that CGP 3466B protects mitochondria which appear to be selectively disrupted in the motoneurons of pmn/pmn mice. The data support evaluation of CGP 3466B as a potential treatment for motor neuron disease.
Mots-clé
Administration, Oral, Animals, Apoptosis/drug effects, Disease Models, Animal, Glial Cell Line-Derived Neurotrophic Factor, Glyceraldehyde-3-Phosphate Dehydrogenases/metabolism, Mice, Mitochondria/drug effects, Motor Neuron Disease/drug therapy, Motor Neuron Disease/mortality, Motor Neurons/drug effects, Nerve Growth Factors, Nerve Tissue Proteins/pharmacology, Oxepins/pharmacology, Weight Loss/drug effects
Pubmed
Web of science
Création de la notice
22/01/2010 9:01
Dernière modification de la notice
20/08/2019 15:52
Données d'usage