title: LIMK1 is involved in the protective effects of bone morphogenetic protein 6 against amyloid-β-induced neurotoxicity in rat hippocampal neurons.
abstract: Bone morphogenetic protein 6 (BMP6) has neuroprotective effects against various neuronal injuries, but its effect on amyloid-β (Aβ)-induced neurotoxicity remains unclear. We exposed rat hippocampal neurons to different concentrations of Aβ25-35 to induce neurotoxicity, and then treated cells with BMP6 to assess the neuroprotective effects. In vivo, we bilaterally injected Aβ1-40 into basal forebrain to simulate the neuropathological process of Alzheimer's disease (AD), and explored changes in the expression of BMP6 and LIMK1. Our data demonstrated that BMP6 prevented apoptosis induced by a high dose of Aβ25-35, and inhibited rod formation induced by low dose of Aβ25-35 in hippocampal neurons. Forebrain injection of Aβ1-40 led to a significant downregulation of BMP6, and inactivation of LIMK1 pathway in basal forebrain, whereas the opposite changes were observed in hippocampus. Our results suggest that BMP6 has neuroprotective effects against Aβ25-35. The BMP6 and LIMK1 pathways may have different expression patterns at different stages of AD, and be self-regulating via a negative feedback mechanism between different brain regions.
authors.affiliation: Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Sun
authors.affiliation: Shanghai First People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Chunni
authors.initials: C
authors.lastname: Guo
authors.affiliation: Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.affiliation: Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Xia
authors.initials: X
authors.lastname: Li
authors.affiliation: Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Guanjun
authors.initials: G
authors.lastname: Li
authors.affiliation: Shanghai Tongji Hospital, Tojing University School of Medicine, Shanghai, China.
authors.forename: Yanli
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Shifu
authors.initials: S
authors.lastname: Xiao
mesh_terms: D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D055418:Bone Morphogenetic Protein 6 / Q000494:pharmacology / Q000627:therapeutic use*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004622:Embryo, Mammalian; D005786:Gene Expression Regulation / Q000187:drug effects*; D006624:Hippocampus / Q000166:cytology; D054461:Lim Kinases / Q000378:metabolism*; D008297:Male; D016501:Neurites / Q000187:drug effects / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D020258:Neurotoxicity Syndromes / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D010446:Peptide Fragments / Q000633:toxicity*; D016548:Prosencephalon / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D016229:Amyloid beta-Peptides; D055418:Bone Morphogenetic Protein 6; D018696:Neuroprotective Agents; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C074636:amyloid beta-protein (25-35); C515892:LIMK1 protein, human; D054461:Lim Kinases
keywords: Alzheimer's disease; actin; amyloid-β; bone morphogenetic protein; rod