Mitotic signaling by β-amyloid causes neuronal death
Mitotic signaling by β-amyloid causes neuronal death
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DOI：
10.1096/fasebj.13.15.2225
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发表时间：
1999-12-01
期刊：
影响因子：
4.8
通讯作者：
Sortino, MA
中科院分区：
文献类型：
--
作者：
Copani, A;Condorelli, F;Sortino, MA
阿尔茨海默病脑内淀粉样斑块的主要成分--β-淀粉样多肽聚集体(Beta AP)以一种尚未明确的机制杀死神经元，导致细胞凋亡。在此，我们报道全长βAP((1-40))或((1-42))及其活性片段βAP((25-35))作为分化的皮质神经元的增殖信号，驱动它们进入细胞周期。该周期遵循了在增殖细胞中观察到的一些步骤，包括诱导周期蛋白D1，视网膜母细胞瘤的磷酸化，以及周期蛋白E和A的诱导，但没有超过S期。细胞周期蛋白依赖性蛋白激酶-4或-2的失活阻止了β-AP((25-35))处理的神经元进入S时相和细胞凋亡的发生。我们的结论是，神经元在屈服于PAP信号之前必须越过G1/S的转变，因此这一通路中的多个步骤可能是神经保护剂的靶点。
Aggregates of beta-amyloid peptide (beta AP), the main constituent of amyloid plaques in Alzheimer's brain, kill neurons by a not yet defined mechanism, leading to apoptotic death, Here, we report that both full-length beta AP((1-40)) or ((1-42)) and its active fragment beta AP((25-35)) act as proliferative signals for differentiated cortical neurons, driving them into the cell cycle. The cycle followed some of the steps observed in proliferating cells, including induction of cyclin D1, phosphorylation of retinoblastoma, and induction of cyclin E and A, but did not progress beyond S phase. Inactivation of cyclin-dependent protein kinase-4 or -2 prevented both the entry into S phase and the development of apoptosis in beta AP((25-35))-treated neurons. We conclude that neurons must cross the G1/S transition before succumbing to PAP signaling, and therefore multiple steps within this pathway may be targets for neuroprotective agents.