Vitamin e inhibits oxidative stress-induced denaturation of nerve terminal proteins involved in neurotransmission

Nozomi Kaneai, Masaya Arai, Hirokatsu Takatsu, Koji Fukui, Shiro Urano

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

One characteristic of age-related neurodegeneration is thought to be cognitive deficits caused by oxidative stress. Neurons in the brain are considered to be particularly vulnerable to oxidative stress, leading to neuronal oxidative damage and neurodegenerative disorders such as Alzheimer's disease (AD) and senile dementia. The process of fusing synaptic plasma membranes and synaptic vesicles involves particular proteins, such as the soluble NSF (N-ethylmaleimide-sensitive factor) attachment protein receptor (SNARE) proteins for docking both membranes, and is integral to neurotransmission. To elucidate whether oxidative stress induces denaturation of SNARE proteins, and whether vitamin E can counteract this process, changes in the expression of synaptobrevin, synaptotagmin, SNAP-25, and syntaxin-1 in rat brain nerve terminals were analyzed using an immunoblotting method. The results showed that oxidative stress induced significant reductions in the levels synaptobrevin and synaptotagmin in synaptic vesicles. Similarly, marked decreases in the levels of SNAP-25 and syntaxin-1 in pre-synaptic plasma membranes were also observed. In the absence of oxidative stress, vitamin E-deficient rats exhibited similar decreases in these proteins. In contrast, it was found that decreases in SNARE proteins, except for SNAP-25, were not observed in vitamin E-supplemented rats, even when the rats were subjected to oxidative stress. These results suggest that reactive oxygen species generated by oxidative stress are detrimental to neurons, resulting in the oxidation of SNARE proteins, thereby disrupting neurotransmission. Additionally, vitamin E is capable of protecting against such neurodegeneration.

Original languageEnglish
Pages (from-to)183-189
Number of pages7
JournalJournal of Alzheimer's Disease
Volume28
Issue number1
DOIs
Publication statusPublished - 2012
Externally publishedYes

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Keywords

  • Neurotransmission
  • oxidative stress
  • SNARE protein
  • synaptic membrane fusion
  • vitamin E

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Geriatrics and Gerontology
  • Clinical Psychology

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