Significance of protein kinase C in the neuropsychotoxicity induced by methamphetamine-like psychostimulants

Eun Joo Shin, Duy Khanh Dang, Young Gwang Hwang, Hai Quyen Tran, Naveen Sharma, Ji Hoon Jeong, Choon Gon Jang, Seung Yeol Nah, Toshitaka Nabeshima, Yukio Yoneda, Jean Lud Cadet, Hyoung Chun Kim

Research output: Contribution to journalReview article

3 Citations (Scopus)

Abstract

The abuse of methamphetamine (MA), an amphetamine (AMPH)-type stimulant, has been demonstrated to be associated with various neuropsychotoxicity, including memory impairment, psychiatric morbidity, and dopaminergic toxicity. Compelling evidence from preclinical studies has indicated that protein kinase C (PKC), a large family of serine/threonine protein kinases, plays an important role in MA-induced neuropsychotoxicity. PKC-mediated N-terminal phosphorylation of dopamine transporter has been identified as one of the prerequisites for MA-induced synaptic dopamine release. Consistently, it has been shown that PKC is involved in MA (or AMPH)-induced memory impairment and mania-like behaviors as well as MA drug dependence. Direct or indirect regulation of factors related to neuronal plasticity seemed to be critical for these actions of PKC. In addition, PKC-mediated mitochondrial dysfunction, oxidative stress or impaired antioxidant defense system has been suggested to play a role in psychiatric and cognitive disturbance induced by MA (or AMPH). In MA-induced dopaminergic toxicity, particularly PKCδ has been shown to trigger oxidative stress, mitochondrial dysfunction, pro-apoptotic changes, and neuroinflammation. Importantly, PKCδ may be a key mediator in the positive feedback loop composed of these detrimental events to potentiate MA-induced dopaminergic toxicity. This review outlines the role of PKC and its individual isozymes in MA-induced neuropsychotoxicity. Better understanding on the molecular mechanism of PKCs might provide a great insight for the development of potential therapeutic or preventive candidates for MA (or AMPH)-associated neuropsychotoxicity.

Original languageEnglish
Pages (from-to)162-170
Number of pages9
JournalNeurochemistry International
Volume124
DOIs
Publication statusPublished - 01-03-2019

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All Science Journal Classification (ASJC) codes

  • Cellular and Molecular Neuroscience
  • Cell Biology

Cite this

Shin, E. J., Dang, D. K., Hwang, Y. G., Tran, H. Q., Sharma, N., Jeong, J. H., Jang, C. G., Nah, S. Y., Nabeshima, T., Yoneda, Y., Cadet, J. L., & Kim, H. C. (2019). Significance of protein kinase C in the neuropsychotoxicity induced by methamphetamine-like psychostimulants. Neurochemistry International, 124, 162-170. https://doi.org/10.1016/j.neuint.2019.01.014