[Inhibition of neuronal death by promoting degradation of intracellular amyloid beta-protein].
Inhibition of aggregation of amyloid p-protein (AP) and promotion of extracellular AM removal are known as potent therapeutic tools for Alzheimer's disease (AD). While, the importance of Af342 accumulating in neurons has recently been suggested, and we have reported that A/42 accumulating in the neurons moves into the nucleus, activating p53 mRNA expression and leading to apoptosis (Ohyagi et al, FASEB J, 2005). Moreover, intraneuronal Ap is reported to induce mitochondrial dysfunction via binding ABAD, synaptic pathology, and inhibition of proteasome. Thus, it is an alternative therapeutic tool to decrease the levels of A342 and p53 proteins in AD neurons. We established a human neuroblastoma (SH-SY5Y) cell culture system in which AV peptide is artificially accumulated in cytosol. We have found that apomorphine hydrochloride promotes degradation of intracellular AM and p53 attenuating oxidative stress-induced apoptosis. Using a proteasome activity assay method, one of the mechanisms is thought to be activation of proteasome. Similar anti-apoptotic effect was observed in the primary cultured neurons. Apomorphine hydrochloride is now used as a dopamine agonist for Parkinson's disease or an anti-ED drug in western countries, but also may be one of the candidate drugs to inhibit neuronal death in AD.
Ohyagi
Yasumasa
Y
Department School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Japan. ohyagi@neuro.med.kyushu-u.ac.jp
Miyoshi
Katsue
K
Ma
Linqing
L
Motomura
Kyoko
K
Kira
Jun-ichi
J
D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D001058:Apomorphine / Q000494:pharmacology; D017209:Apoptosis; D006801:Humans; D009474:Neurons / Q000166:cytology*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism
D016229:Amyloid beta-Peptides; D016159:Tumor Suppressor Protein p53; D046988:Proteasome Endopeptidase Complex; D001058:Apomorphine