title: Glyceraldehyde-3-phosphate dehydrogenase aggregation inhibitor peptide: A potential therapeutic strategy against oxidative stress-induced cell death.
abstract: The glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) has multiple functions, including mediating oxidative stress-induced neuronal cell death. This process is associated with disulfide-bonded GAPDH aggregation. Some reports suggest a link between GAPDH and the pathogenesis of several oxidative stress-related diseases. However, the pathological significance of GAPDH aggregation in disease pathogenesis remains unclear due to the lack of an effective GAPDH aggregation inhibitor. In this study, we identified a GAPDH aggregation inhibitor (GAI) peptide and evaluated its biological profile. The decapeptide GAI specifically inhibited GAPDH aggregation in a concentration-dependent manner. Additionally, the GAI peptide did not affect GAPDH glycolytic activity or cell viability. The GAI peptide also exerted a protective effect against oxidative stress-induced cell death in SH-SY5Y cells. This peptide could potentially serve as a tool to investigate GAPDH aggregation-related neurodegenerative and neuropsychiatric disorders and as a possible therapy for diseases associated with oxidative stress-induced cell death.
authors.affiliation: Laboratory of Veterinary Pharmacology, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, 1-58, Rinkuourai-kita, Izumisano, Osaka, 5988531, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Itakura
authors.affiliation: Laboratory of Veterinary Pharmacology, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, 1-58, Rinkuourai-kita, Izumisano, Osaka, 5988531, Japan. Electronic address: hnakajima@vet.osakafu-u.ac.jp.
authors.forename: Hidemitsu
authors.initials: H
authors.lastname: Nakajima
authors.affiliation: Laboratory of Veterinary Pharmacology, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, 1-58, Rinkuourai-kita, Izumisano, Osaka, 5988531, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Semi
authors.affiliation: Laboratory of Veterinary Pharmacology, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, 1-58, Rinkuourai-kita, Izumisano, Osaka, 5988531, Japan.
authors.forename: Shusaku
authors.initials: S
authors.lastname: Higashida
authors.affiliation: Laboratory of Veterinary Pharmacology, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, 1-58, Rinkuourai-kita, Izumisano, Osaka, 5988531, Japan.
authors.forename: Yasu-Taka
authors.initials: YT
authors.lastname: Azuma
authors.affiliation: Laboratory of Veterinary Pharmacology, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, 1-58, Rinkuourai-kita, Izumisano, Osaka, 5988531, Japan.
authors.forename: Tadayoshi
authors.initials: T
authors.lastname: Takeuchi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D020134:Catalytic Domain; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D004926:Escherichia coli / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006019:Glycolysis / Q000187:drug effects; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009842:Oligopeptides / Q000138:chemical synthesis / Q000494:pharmacology*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D016716:PC12 Cells; D066329:Protein Aggregates / Q000187:drug effects*; D011485:Protein Binding; D051381:Rats; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D009842:Oligopeptides; D066329:Protein Aggregates; D011994:Recombinant Proteins; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases
keywords: Cell death; GAPDH; Inhibitor; Protein aggregation; Therapeutics