Inhibition of neuronal death by promoting degradation of intracellular amyloid β-protein

Yasumasa Ohyagi, Katsue Miyoshi, Linqing Ma, Kyoko Motomura, Jun Ichi Kira

Research output: Contribution to journalReview article

Abstract

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.

Original languageEnglish
Pages (from-to)57-62
Number of pages6
JournalJapanese Journal of Neuropsychopharmacology
Volume27
Issue number2
Publication statusPublished - Apr 1 2007

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Amyloidogenic Proteins
Proteasome Endopeptidase Complex
Neurons
Alzheimer Disease
Apomorphine
Apoptosis
Serum Amyloid A Protein
Dopamine Agonists
Neuroblastoma
Pharmaceutical Preparations
Cytosol
Parkinson Disease
Oxidative Stress
Cell Culture Techniques
Pathology
Messenger RNA
Peptides
Inhibition (Psychology)
Therapeutics
Proteins

All Science Journal Classification (ASJC) codes

  • Clinical Psychology
  • Pharmacology
  • Psychiatry and Mental health
  • Pharmacology (medical)

Cite this

Inhibition of neuronal death by promoting degradation of intracellular amyloid β-protein. / Ohyagi, Yasumasa; Miyoshi, Katsue; Ma, Linqing; Motomura, Kyoko; Kira, Jun Ichi.

In: Japanese Journal of Neuropsychopharmacology, Vol. 27, No. 2, 01.04.2007, p. 57-62.

Research output: Contribution to journalReview article

Ohyagi, Yasumasa ; Miyoshi, Katsue ; Ma, Linqing ; Motomura, Kyoko ; Kira, Jun Ichi. / Inhibition of neuronal death by promoting degradation of intracellular amyloid β-protein. In: Japanese Journal of Neuropsychopharmacology. 2007 ; Vol. 27, No. 2. pp. 57-62.
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