Alguacil Luis F, Herradón Gonzalo
Lab. Pharmacology, Faculty of Pharmacy, Universidad CEU San Pablo, Urb. Montepríncipe, 28668 Boadilla del Monte, Madrid, Spain.
Recent Pat CNS Drug Discov. 2015;10(1):28-33. doi: 10.2174/1574889810666150326103916.
Pleiotrophin (PTN) and Midkine (MK) are neurotrophines with documented protective actions in experimental models of neurodegenerative diseases and beneficial effects on toxicity and addictive behaviours related to drug abuse. Concerning the latter, both PTN and MK prevent the neurotoxic effects of amphetamine on nigrostriatal pathways and endogenous PTN also limits amphetamine reward. Moreover, endogenous PTN overexpression in the prefontral cortex abolishes alcohol- induced conditioned place preference. This review summarizes the existing patents for using PTN and MK in the treatment and diagnosis of neuropsychiatric disorders with a focus on neurotoxicity, neurodegeneration and substance use disorders. We have also reviewed the mechanism of action of PTN and MK and summarized existing patents on downstream modulators in their signaling pathways for the same indications.
多效生长因子(PTN)和中期因子(MK)是神经营养因子,在神经退行性疾病的实验模型中具有已被证实的保护作用,并且对与药物滥用相关的毒性和成瘾行为具有有益影响。关于后者,PTN和MK均能预防苯丙胺对黑质纹状体通路的神经毒性作用,内源性PTN还能限制苯丙胺奖赏。此外,前额叶皮质中内源性PTN的过表达可消除酒精诱导的条件性位置偏爱。本综述总结了使用PTN和MK治疗和诊断神经精神疾病的现有专利,重点关注神经毒性、神经退行性变和物质使用障碍。我们还综述了PTN和MK的作用机制,并总结了针对相同适应症的其信号通路中下游调节剂的现有专利。