帕金森病的神经保护治疗.ppt

帕金森病的神经保护治疗
一. PD的概述
Parkinson’s Disease的病理生理学
Management of Parkinson’s Disease
基于PD 病理机制的神经保护策略
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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 ; 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(., mild to severe memory impairment), 情绪改变(., depression, apathy and anxiety), 睡眠紊乱(., insomnia, hypersomnia, rapid eye movement sleep behavior disorder, sleep apnea), 自主神经障碍(., bladder disturbances, orthostatic hypotension, sweating), 感觉症状(., pain, visual and olfactory deficits, paresthesia) and 胃肠功能失调(., constipation, nausea, dysphagia) (Barone 2010; Bastide et al. 2015; Bohnen and Albin 2011; Huot et al. 2013; Schaeffer et al. 2014).
Perez XA. Preclinical Evidence for a Role of the Nicotinic Cholinergic System in Parkinson's Disease. Neuropsychol Rev. 2015 .
（一）Parkinson’s Disease – 简介
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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).
Perez XA. Preclinical Evidence for a Role of the Nicotinic Cholinergic System in Parkinson's Disease. Neuropsychol Rev. 2015 .
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目前的治疗方案，重点采用DA替代疗法增加DA传输和平衡-