Troglitazone inhibits both post-glutamate neurotoxicity and low-potassium-induced apoptosis in cerebellar granule neurons - PubMed (original) (raw)

Troglitazone inhibits both post-glutamate neurotoxicity and low-potassium-induced apoptosis in cerebellar granule neurons

Shigeko Uryu et al. Brain Res. 2002.

Abstract

Both excitotoxicity and apoptosis contribute to neuronal loss in various neurodegenerative diseases such as Alzheimer's disease as well as stroke, and a drug inhibiting both types of cell death may lead to practical treatment for these diseases. Post-treatment with troglitazone, a potent and specific activator of peroxisome proliferator-activated receptor (PPAR)-gamma attenuated the cell death of cerebellar granule neurons, triggered by glutamate exposure. The inhibitory effect of troglitazone against glutamate excitotoxicity, in vitro, was observed even when added 2.5 h after the end of glutamate exposure, a time when glutamate antagonists are no longer neuroprotective. However, troglitazone did not block the glutamate-induced elevation of calcium influx, suggesting that troglitazone interfered with downstream consequences of excitotoxic glutamate receptor overactivation. In addition, troglitazone also suppressed low-potassium-induced apoptosis in cerebellar granule neurons in a phosphatidylinositol 3-kinase independent manner. In conclusion, although the mechanisms of troglitazone's neuroprotective effects are unknown, the post-treatment-neuroprotective effect and the dual-inhibitory-activity against both excitotoxicity and apoptosis may provide a novel therapy for various neurodegenerative diseases.

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