水Soluble oligomerAmyloid fibrilMonomerADDLSDprotofibrilABPglobulomer,etc.a-helixorB-sheetβ-sheetrandom coilInsoluble-SolubleSolubleLesstoxic-ToxicNontoxicBApoEEstradiolMembrane fluidityMembrane potentialOPCOPSFoodsNeurosteroidsOCholesterolRaft(ganglioside,etc.Formation of amyloid channel(C)Disruption of CahomeostasisFree radial formationPhosphorylationoftau,etc.DegenerationofsynapsesNeuronaldeathAlzheimer's diseaseMasahiroKetal.zoo0
β-Amyloid protein (Aβ)-channel hypothesis Masahiro K, et al. 2000
WashControlAB(1-40)700pA150msRC200nMAβ(1-40)2.21.02.0OControl口200nM Aβ(1-40)1.80,51.60,0OOOOO1.420-80-60-4020-406080HVe(mV)-0,51.01.00.860-10102030050Rovira C,etal2002Time(min
Aβ(1–40) increases the amplitude of high voltage activated calcium channels Rovira C, et al. 2002
Aβmutant PSEndogenousAmyloidRyRInsP3RPlasmalemmalChannellon ChannelsDysregulationof CaHomeostasisAlzheimerSDisease
Conclusion mutant PS RyR InsP3R Aβ Amyloid Channel Endogenous Plasmalemmal Ion Channels Dysregulation of Ca Homeostasis Alzheimer ’s Disease
ChanSL,MayneM,HoldenCP,GeigerJD,andMattsonMP.JBiolChem2000:275:18195-18200.2. Cheung KH, Mei L, Don-On Daniel Mak, Hayashi I,Iwatsubo K, Kang DE, and Foskett JK. Sci Signal 2010;3(114): ra22.3.Masahiro K and Yoichiro K.Brain Research Bulletin2000; 53(4): 389-3974. Demuro A, Parker I, and Stutzmann GE. J Biol Chem2010:285:12463-124685. Rovira C, Arbez N, and Mariani J. Biochemical andBiophysicalResearchCommunications2002;296:13171321
Reference 1. Chan SL, Mayne M, Holden CP, Geiger JD, and Mattson MP. J Biol Chem 2000;275:18195–18200. 2. Cheung KH, Mei L, Don-On Daniel Mak, Hayashi I, Iwatsubo K, Kang DE, and Foskett JK. Sci Signal 2010; 3(114): ra22. 3. Masahiro K and Yoichiro K. Brain Research Bulletin 2000; 53(4): 389–397. 4. Demuro A, Parker I, and Stutzmann GE. J Biol Chem 2010;285:12463–12468. 5. Rovira C, Arbez N, and Mariani J. Biochemical and Biophysical Research Communications 2002;296:1317– 1321
癫痫神经系统离子通道病吕秉华
神经系统离子通道病 癫痫 吕秉华