title: Methyl 3,4-dihydroxybenzoate protects primary cortical neurons against Aβ₂₅₋₃₅-induced neurotoxicity through mitochondria pathway.
abstract: Amyloid-β peptides (Aβ), 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 Aβ-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 μM Aβ25-35 for 24 hr. The results showed that Aβ25-35 could induce neurotoxicity as evidenced by the decreased cell viability and the increased apoptotic rate. In parallel, Aβ25-35 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 Aβ25-35 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 Aβ25-35 -treated primary cortical neurons. All these results were beneficial in their protective effect against Aβ-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.
authors.affiliation: Department of Pharmacology, School of Medicine, Jinan University, Guangzhou, China.
authors.forename: Xiao-Wen
authors.initials: XW
authors.lastname: Zhou
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zhang
authors.forename: Chao-Fen
authors.initials: CF
authors.lastname: Su
authors.forename: Ruo-Hua
authors.initials: RH
authors.lastname: Lv
authors.forename: Xing
authors.initials: X
authors.lastname: Zhou
authors.forename: Liang
authors.initials: L
authors.lastname: Cai
authors.forename: Chen-Yu
authors.initials: CY
authors.lastname: Wang
authors.forename: Li
authors.initials: L
authors.lastname: Yan
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: Huan-Min
authors.initials: HM
authors.lastname: Luo
mesh_terms: D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D020169:Caspases / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000187:drug effects; D062385:Hydroxybenzoates / Q000494:pharmacology*; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects* / Q000648:ultrastructure*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010446:Peptide Fragments / Q000633:toxicity*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C520290:3,4-dihydroxybenzoate; D016229:Amyloid beta-Peptides; D062385:Hydroxybenzoates; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; C075222:amyloid beta-protein (1-42); D051028:bcl-2-Associated X Protein; D020169:Caspases; D020782:Matrix Metalloproteinases
keywords: Alzheimer's disease; amyloid-β peptides; apoptosis; neurons; neuroprotection