Mitotic signaling by beta-amyloid causes neuronal death.
نویسندگان
چکیده
Aggregates of beta-amyloid peptide (betaAP), 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 betaAP((1-40)) or ((1-42)) and its active fragment betaAP((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 betaAP((25-35))-treated neurons. We conclude that neurons must cross the G1/S transition before succumbing to betaAP signaling, and therefore multiple steps within this pathway may be targets for neuroprotective agents.-Copani, A., Condorelli, F., Caruso, A., Vancheri, C., Sala, A., Giuffrida Stella, A. M., Canonico, P. L., Nicoletti, F., Sortino, M. A. Mitotic signaling by beta-amyloid causes neuronal death.
منابع مشابه
P 102: The Study of Some Factors Which Effect on Beta-Amyloid Signaling in Neuroinflammation
Neurological inflammatory diseases are developing rapidly. Different factors involved in the pathogenesis of these diseases. In this article, we discuss some of the mechanisms are dealt with. An aberrant procedure of beta-amyloid precursor protein (BAPP) to form neurotoxic beta-amyloid peptides and an accumulated insoluble polymer of beta –amyloid (BA) that forms the senile plaque. The ab...
متن کاملP135: The Role of Amyloid Beta-Peptides and Tau Protein in Alzheimer\'s Disease
Alzheimer's desease is the most common age-related neurodegenerative disorder, and cognitive problems such as defects in learning and memory are of its symptoms. Among the factors involved in the pathogenesis of the disease are biochemical disorders in protein production, oxidative stress, decreased acetylcholine secretion and inflammation of the brain tissue. Extra-neuronal accumulation ...
متن کاملIntegrins mediate beta-amyloid-induced cell-cycle activation and neuronal death.
Early intracellular events responsible for cell-cycle induction by beta-amyloid (A beta) in neurons have not been identified yet. Extracellular signal-regulated kinases 1/2 (ERK1/2) have been identified in this pathway, and inhibition of ERK activity prevents cell-cycle activation and reduces neuronal death induced by A beta. To identify upstream events responsible for ERK activation, attention...
متن کاملSignaling events in amyloid beta-peptide-induced neuronal death and insulin-like growth factor I protection.
Amyloid beta-peptide (Abeta) is implicated as the toxic agent in Alzheimer's disease and is the major component of brain amyloid plaques. In vitro, Abeta causes cell death, but the molecular mechanisms are unclear. We analyzed the early signaling mechanisms involved in Abeta toxicity using the SH-SY5Y neuroblastoma cell line. Abeta caused cell death and induced a 2- to 3-fold activation of JNK....
متن کاملInhibition of UDP/P2Y6 purinergic signaling prevents phagocytosis of viable neurons by activated microglia in vitro and in vivo
Microglia activated through Toll-like receptor (TLR)-2 or -4 can cause neuronal death by phagocytosing otherwise-viable neurons-a form of cell death called "phagoptosis." UDP release from neurons has been shown to provoke microglial phagocytosis of neurons via microglial P2Y6 receptors, but whether inhibition of this process affects neuronal survival is unknown. We tested here whether inhibitio...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- FASEB journal : official publication of the Federation of American Societies for Experimental Biology
دوره 13 15 شماره
صفحات -
تاریخ انتشار 1999