| Summary: | 碩士 === 國立陽明大學 === 神經科學研究所 === 91 === Alzheimer's disease is a progressive and fatal neurodegenerative disorder and has become a serious problem with the increasing age of the world population. Amyloid β peptide (Aβ) has been implicated to mediate neuronal degeneration. We used primary rat cortical neurons to explore the mechanisms involved in Aβ-induced cell death. Aβ25—35 results in apoptosis of cultured rat cortical neurons. We have examined whether MAPK and caspase 8 are involved in Aβ25—35-mediated neuronal cell death by using inhibitors of ERK, p38 MAPK, and JNK. We found that Aβ25—35-induced neuronal cell death was inhibited by SP600125, the specific inhibitor of JNK, but not by SB203580 or PD98059. Inhibition of caspase 8 also did not prevent Aβ25—35-induced neuronal cell death. We also found that cytochrome c release and mitochondrial membrane potential (ΔΨm) loss were involved in Aβ25—35-mediated cortical neuron apoptosis. The mechanisms of Aβ25—35-induced cytochrome c release and ΔΨm loss are yet unknown. Because inhibition of the mitochondrial permeability transition pore (mPTP) with bongkrekic acid had no effects on cell survival of Aβ25—35-treated neurons, Aβ25—35-induced cytochrome c release and ΔΨm loss may not be mediated by mPTP opening. Additionally, kaempferol prevented Aβ25—35-induced cell death and increased ΔΨm which may account for the significant neuroprotection of kaempferol.
|
|---|
