| | |  | | | | Record from Web of Science® | | | | | | |
| Caspase-8 is an effector in apoptotic death of dopaminergic neurons in Parkinson's disease, but pathway inhibition results in neuronal necrosis |
|
|
| Author(s): Hartmann A, Troadec JD, Hunot S, Kikly K, Faucheux BA, Mouatt-Prigent A, Ruberg M, Agid Y, Hirsch EC |
| Source: JOURNAL OF NEUROSCIENCE Volume: 21 Issue: 7 Pages: 2247-2255 Published: APR 1 2001 |
| Times Cited: 113 References: 57 |
| Abstract: Caspase-8 is a proximal effector protein of the tumor necrosis factor receptor family death pathway. In the present human postmortem study, we observed a significantly higher percentage of dopaminergic (DA) substantia nigra pars compacta neurons that displayed caspase-8 activation in Parkinson's disease (PD) patients compared with controls. In an in vivo experimental PD model, namely subchronically 1,2,3,6-tetrahydropyridinetreated mice, we also show that caspase-8 is indeed activated after exposure to this toxin early in the course of cell demise, suggesting that caspase-8 activation precedes and is not the consequence of cell death. However, cotreatment of 1-methyl-4-phenylpyridinium-intoxicated primary DA cultures with broad-spectrum and specific caspase-8 inhibitors did not result in neuroprotection but seemed to trigger a switch from apoptosis to necrosis. We propose that this effect is related to ATP depletion and suggest that the use of caspase inhibitors in pathologies linked to intracellular energy depletion, such as PD, should be cautiously evaluated. |
| Document Type: Article |
| Language: English |
| Reprint Address: Hirsch, EC (reprint author), Hop La Pitie Salpetriere, INSERM, U289, 47 Blvd Hop, F-75013 Paris, France |
Addresses:
1. Hop La Pitie Salpetriere, INSERM, U289, F-75013 Paris, France
2. SmithKline Beecham Pharmaceut, King Of Prussia, PA 19406 USA |
| Publisher: SOC NEUROSCIENCE, 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA |
| Subject Category: Neurosciences |
| IDS Number: 415RU |
| ISSN: 0270-6474 |
|
| | | | | | | | | Record from Web of Science® | | | | | | | | | |