Methyl 3,4-dihydroxybenzoate protects primary cortical neurons against A beta(25-35)-induced neurotoxicity through mitochondria pathway

作者：Zhou Xiao Wen; Zhang Zheng; Su Chao Fen; Lv Ruo Hua; Zhou Xing; Cai Liang; Wang Chen Yu; Yan Li; Zhang Wei; Luo Huan Min^*

来源：Journal of Neuroscience Research, 2013, 91(9): 1215-1225.

DOI：10.1002/jnr.23235

• Alzheimer's disease
• amyloid- peptides
• neuroprotection
• neurons
• apoptosis

Amyloid- peptides (A), which can aggregate into oligomers or fibrils in neurons, play a critical role in the pathogenesis of Alzheimer's disease (AD). Methyl 3,4-dihydroxybenzoate (MDHB), a phenolic acid compound, has been reported to have antioxidative and neurotrophic effects. The present study investigated the neuroprotective effects of MDHB against A-induced apoptosis in rat primary cortical neutons. The primary cortical neurons were pretreated with different concentrations of MDHB for 24 hr, then incubated with 10 M A(25-35) for 24 hr. The results showed that A(25-35) could induce neurotoxicity as evidenced by the decreased cell viability and the increased apoptotic rate. In parallel, A(25-35) significantly increased the reactive oxygen species accumulation and decreased mitochondrial membrane potential. However, pretreatment of the primary cortical neurons with MDHB could effectively suppress these cellular events caused by A(25-35) exposure. In addition, MDHB could increase the level of Bcl-2, decrease the level of Bax, and inhibit the activation of caspase-9 and caspase-3 in A(25-35)-treated primary cortical neurons. All these results were beneficial in their protective effect against A-induced neurotoxicity. Our results suggest that MDHB has a neuroprotective effect that provides a pharmacological basis for its clinical use in the treatment of AD.

• 单位
  1; 香港大学