TY - JOUR
T1 - Inhibition of neuronal death by promoting degradation of intracellular amyloid β-protein
AU - Ohyagi, Yasumasa
AU - Miyoshi, Katsue
AU - Ma, Linqing
AU - Motomura, Kyoko
AU - Kira, Jun Ichi
PY - 2007/4
Y1 - 2007/4
N2 - Inhibition of aggregation of amyloid β-protein (Aβ) and promotion of extracellular Aβ removal are known as potent therapeutic tools for Alzheimer's disease (AD). While, the importance of Aβ42 accumulating in neurons has recently been suggested, and we have reported that Aβ42 accumulating in the neurons moves into the nucleus, activating p53 mRNA expression and leading to apoptosis (Ohyagi et al, FASEB J, 2005). Moreover, intraneuronal Aβ 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 Aβ42 and p53 proteins in AD neurons. We established a human neuroblastoma (SH-SY5Y) cell culture system in which Aβ peptide is artificially accumulated in cytosol. We have found that apomorphine hydrochloride promotes degradation of intracellular Aβ 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.
AB - Inhibition of aggregation of amyloid β-protein (Aβ) and promotion of extracellular Aβ removal are known as potent therapeutic tools for Alzheimer's disease (AD). While, the importance of Aβ42 accumulating in neurons has recently been suggested, and we have reported that Aβ42 accumulating in the neurons moves into the nucleus, activating p53 mRNA expression and leading to apoptosis (Ohyagi et al, FASEB J, 2005). Moreover, intraneuronal Aβ 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 Aβ42 and p53 proteins in AD neurons. We established a human neuroblastoma (SH-SY5Y) cell culture system in which Aβ peptide is artificially accumulated in cytosol. We have found that apomorphine hydrochloride promotes degradation of intracellular Aβ 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.
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M3 - Review article
C2 - 17515111
AN - SCOPUS:34249001676
SN - 1340-2544
VL - 27
SP - 57
EP - 62
JO - Japanese Journal of Neuropsychopharmacology
JF - Japanese Journal of Neuropsychopharmacology
IS - 2
ER -