Wang, Yifan published the artcileInvolvement of p75NTR in the effects of Aβ on L-type Ca2+ channel in cultured neuronal networks, Safety of Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, the main research area is NTR calcium channel cultured neuronal network; AD; Aβ; L-type Ca(2+) channel; p75NTR.
Ca2+ overload in neurons has been implicated in Alzheimer’s Disease (AD). Upregulation of Ca2+ through L-type Ca2+ channels was known to be involved in the neurodegeneration induced by amyloid-β (Aβ) peptides in AD. However, little is known about the mechanism by which upregulation of L-type Ca2+ channel currents is linked to Aβ-induced neuronal toxicity. In the present study, we found that the L-type Ca2+ current in transgenic AD mice (Tg2576) neurons is greater than in wild-type (WT) neurons, and this Ca2+ channel current change were rescued in Tg2576/p75NTR+/- (p75 neurotrophin receptor) neurons. We further examined the changes in the gating of L-type Ca2+ channels following Aβ42 treatment, and the results showed that the L-type Ca2+ channel current was significantly increased by Aβ42 treatment in WT hippocampal neurons. Blocking or decreasing the expression of p75NTR eliminated the influence of Aβ42 on the L-type Ca2+ channel current in WT hippocampal neurons. We also evaluated how Aβ42 affected the voltage-dependent activation and inactivation of L-type Ca2+ channels in cultured WT neurons. The results indicated that the half-maximal activation voltage (V1/2) was left shifted, and the half-inactivation voltage (V1/2) displayed a right shift in neuron treated by Aβ42. Decreasing the expression of p75NTR eliminated the effect of Aβ42 on voltage-dependent activation and inactivation of the L-type Ca2+ channel. These results indicate that Aβ42 changes L-type Ca2+ channel currents by modulating the channel’s activation and inactivation dynamics, while decreasing p75NTR expression can remove this effect.
Life Sciences published new progress about Alzheimer disease. 21829-25-4 belongs to class pyridine-derivatives, name is Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate, and the molecular formula is C17H18N2O6, Safety of Dimethyl 2,6-dimethyl-4-(2-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate.