Fu_2006_J.Neurochem_98_1400

Reference

Title : Bis(7)-tacrine attenuates beta amyloid-induced neuronal apoptosis by regulating L-type calcium channels - Fu_2006_J.Neurochem_98_1400
Author(s) : Fu H , Li W , Lao Y , Luo J , Lee NT , Kan KK , Tsang HW , Tsim KWK , Pang Y , Li Z , Chang DC , Li M , Han Y
Ref : Journal of Neurochemistry , 98 :1400 , 2006
Abstract : Beta amyloid protein (Abeta) and acetylcholinesterase (AChE) have been shown to be closely implicated in the pathogenesis of Alzheimer's disease. In the current study, we investigated the effects of bis(7)-tacrine, a novel dimeric AChE inhibitor, on Abeta-induced neurotoxicity in primary cortical neurons. Bis(7)-tacrine, but not other AChE inhibitors, elicited a marked reduction of both fibrillar and soluble oligomeric forms of Abeta-induced apoptosis as evidenced by chromatin condensation and DNA specific fragmentation. Both nicotinic and muscarinic receptor antagonists failed to block the effects of bis(7)-tacrine. Instead, nimodipine, a blocker of L-type voltage-dependent Ca2+ channels (VDCCs), attenuated Abeta neurotoxicity, whereas N-, P/Q- or R-type VDCCs blockers and ionotropic glutamate receptor antagonists did not. Fluorescence Ca2+ imaging assay revealed that, similar to nimodipine, bis(7)-tacrine reversed Abeta-triggered intracellular Ca2+ increase, which was mainly contributed by the extracellular Ca2+ instead of endoplasmic reticulum and mitochondria Ca2+. Concurrently, using whole cell patch-clamping technique, it was found that bis(7)-tacrine significantly reduced the augmentation of high voltage-activated inward calcium currents induced by Abeta. These results suggest that bis(7)-tacrine attenuates Abeta-induced neuronal apoptosis by regulating L-type VDCCs, offers a novel modality as to how the agent exerts neuroprotective effects.
ESTHER : Fu_2006_J.Neurochem_98_1400
PubMedSearch : Fu_2006_J.Neurochem_98_1400
PubMedID: 16771827

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Citations formats

Fu H, Li W, Lao Y, Luo J, Lee NT, Kan KK, Tsang HW, Tsim KWK, Pang Y, Li Z, Chang DC, Li M, Han Y (2006)
Bis(7)-tacrine attenuates beta amyloid-induced neuronal apoptosis by regulating L-type calcium channels
Journal of Neurochemistry 98 :1400

Fu H, Li W, Lao Y, Luo J, Lee NT, Kan KK, Tsang HW, Tsim KWK, Pang Y, Li Z, Chang DC, Li M, Han Y (2006)
Journal of Neurochemistry 98 :1400