帕金森病的神经保护治疗王训PPT课件.ppt

帕金森病的神经保护治疗Neuroprotection Therapy in Parkinson’s Disease;内容;一. PD的概述;Parkinson’s disease (PD) is 第二大neurodegenerative disorder 在全球65 岁以上 人群(Bertram and Tanzi 2005). PD的主要神经功能损害 ：由于黑质致密部(SNc) 的DA神经元缺失→ 纹状体(DA) 功能缺损→运动障碍(like akinesia, rigidity, resting tremor and postural instability) (Di Monte et al.2000; Meissner et al. 2011; Obeso et al. 2004, 2010;Schapira and Jenner 2011; Wichmann et al. 2011; Wullner et al. 1994). In addition, DA和其他神经递质变性→非运动症状：认知障碍(e.g., mild to severe memory impairment), 情绪改变(e.g., depression, apathy and anxiety), 睡眠紊乱(e.g., insomnia, hypersomnia, rapid eye movement sleep behavior disorder, sleep apnea), 自主神经障碍(e.g., bladder disturbances, orthostatic hypotension, sweating), 感觉症状(e.g., pain, visual and olfactory deficits, paresthesia) and 胃肠功能失调(e.g., constipation, nausea, dysphagia) (Barone 2010; Bastide et al. 2015; Bohnen and Albin 2011; Huot et al. 2013; Schaeffer et al. 2014).;90% of PD 散发型, with risk factors such as age, drug abuse, and gene-environment interactions known to contribute to this form of PD (Blesa and Przedborski 2014; Hirsch et al. 2013; Terzioglu and Galter 2008; Valadas et al. 2015). 10 % of PD 家族型linked to genetic mutations (Blesa and Przedborski 2014; Hirsch et al. 2013; Terzioglu and Galter 2008; Valadas et al. 2015). Interestingly,基因组学的关联研究已经表明，一些家族性PD的关联基因也可能是散发型PD的危险因素 (Lesage and Brice 2009). 这些研究+家族性与散发性PD的很强相似性，说明PD受损的途径可能是相似的或重叠的。几十年来，PD的病理研究重点在黑质-纹状体DA能通路的神经退变→运动症状. However, PD是一种异质性疾病，影响多种神经递质系统和多种脑环路→患者的运动和非运动症状；事实上，过去的十年已明确5-HT，NA，Glu，γ-GABA，和Choline能系统已参与其中. (Barone 2010; Bastide et al. 2015; Huot et al. 2013). ;目前的治疗方案，重点采用DA替代疗法增加DA传输和平衡-治疗DA能神经元变性引起的运动障碍。 然而，这种策略会导致不同的副作用，如运动波动、异常不自主运动或L-dopa诱导的运动障碍(LIDs). 鉴于PD患病率日益增加，而可用治疗方法有限，继续研究关注于揭示???金森病的分子缺陷，以开发新的靶向治疗。;;A diagram depicting possible pathogenic events in PD. A hypothetical series of molecular events likely contributing to PD pathogenesis is diagrammed. Potential sites of action by the neuroprotective agents used in this study are indicated.;帕