Chilumuri Amrutha, Milton Nathaniel G N
Department of Human and Health Sciences, School of Life Sciences, University of Westminster, 115 New Cavendish Street, London W1W 6UW, UK.
Department of Human and Health Sciences, School of Life Sciences, University of Westminster, 115 New Cavendish Street, London W1W 6UW, UK ; Health Sciences Research Centre, University of Roehampton, Holybourne Avenue, London SW15 4JD, UK.
ISRN Neurosci. 2013 Jul 17;2013:253210. doi: 10.1155/2013/253210. eCollection 2013.
Recent studies have suggested that the kisspeptin (KP) and kissorphin (KSO) peptides have neuroprotective actions against the Alzheimer's amyloid- β (A β ) peptide. Overexpression of the human KiSS-1 gene that codes for KP and KSO peptides in SH-SY5Y neurons has also been shown to inhibit A β neurotoxicity. The in vivo actions of KP include activation of neuroendocrine and neurotransmitter systems. The present study used antagonists of KP, neuropeptide FF (NPFF), opioids, oxytocin, estrogen, adrenergic, cholinergic, dopaminergic, serotonergic, and γ -aminobutyric acid (GABA) receptors plus inhibitors of catalase, cyclooxygenase, nitric oxide synthase, and the mitogen activated protein kinase cascade to characterize the KiSS-1 gene overexpression neuroprotection against A β cell model. The results showed that KiSS-1 overexpression is neuroprotective against A β and the action appears to involve the KP or KSO peptide products of KiSS-1 processing. The mechanism of neuroprotection does not involve the activation of the KP or NPFF receptors. Opioids play a role in the toxicity of A β in the KiSS-1 overexpression system and opioid antagonists naloxone or naltrexone inhibited A β toxicity. The mechanism of KiSS-1 overexpression induced protection against A β appears to have an oxytocin plus a cyclooxygenase dependent component, with the oxytocin antagonist atosiban and the cyclooxygenase inhibitor SC-560 both enhancing the toxicity of A β .
最近的研究表明，亲吻素（KP）和亲吻孤儿肽（KSO）对阿尔茨海默病的淀粉样β（Aβ）肽具有神经保护作用。在SH-SY5Y神经元中编码KP和KSO肽的人类KiSS-1基因的过表达也已显示出可抑制Aβ神经毒性。KP的体内作用包括激活神经内分泌和神经递质系统。本研究使用了KP拮抗剂、神经肽FF（NPFF）、阿片类药物、催产素、雌激素、肾上腺素能、胆碱能、多巴胺能、5-羟色胺能和γ-氨基丁酸（GABA）受体拮抗剂，以及过氧化氢酶、环氧化酶、一氧化氮合酶和丝裂原活化蛋白激酶级联反应的抑制剂，来表征KiSS-1基因过表达对Aβ细胞模型的神经保护作用。结果表明，KiSS-1过表达对Aβ具有神经保护作用，且该作用似乎涉及KiSS-1加工产生的KP或KSO肽产物。神经保护机制不涉及KP或NPFF受体的激活。阿片类药物在KiSS-1过表达系统中Aβ的毒性中起作用，阿片类拮抗剂纳洛酮或纳曲酮可抑制Aβ毒性。KiSS-1过表达诱导的对Aβ的保护机制似乎有一个催产素加环氧化酶依赖性成分，催产素拮抗剂阿托西班和环氧化酶抑制剂SC-560均增强了Aβ的毒性。
