Faculty of Science, Engineering and Built Environment, School of Life and Environmental Sciences, Deakin University, Waurn Ponds, Victoria, 3216, Australia.
Faculty of Health, School of Medicine, Deakin University, Waurn Ponds, Victoria, 3216, Australia.
Mol Neurobiol. 2020 Nov;57(11):4878-4890. doi: 10.1007/s12035-020-02054-6. Epub 2020 Aug 19.
Neurodegeneration leading to Parkinson's disease (PD) and Alzheimer's disease (AD) has become a major health burden globally. Current treatments mainly target controlling symptoms and there are no therapeutics available in clinical practice to preventing the neurodegeneration or inducing neuronal repairing. Thus, the demand of novel research for the two disorders is imperative. This literature review aims to provide a collection of published work on PD and AD and current uses of endocannabinoid system (ECS) as a potential drug target for neurodegeneration. PD is frequently treated with L-DOPA and deep brain stimulation. Recent gene modification and remodelling techniques, such as CRISPR through human embryonic stem cells and induced pluripotent stem cells, have shown promising strategy for personalised medicine. AD characterised by extracellular deposits of amyloid β-senile plaques and neurofibrillary tangles of tau protein commonly uses choline acetyltransferase enhancers as therapeutics. The ECS is currently being studied as PD and AD drug targets where overexpression of ECS receptors exerted neuroprotection against PD and reduced neuroinflammation in AD. The delta-9-tetrahydrocannabinoid (Δ-THC) and cannabidiol (CBD) cannabinoids of plant Cannabis sativa have shown neuroprotection upon PD and AD animal models yet triggered toxic effects on patients when administered directly. Therefore, understanding the precise molecular cascade following cannabinoid treatment is suggested, focusing especially on gene expression to identify drug targets for preventing and repairing neurodegeneration.
神经退行性病变导致的帕金森病 (PD) 和阿尔茨海默病 (AD) 已成为全球主要的健康负担。目前的治疗方法主要针对控制症状,临床上尚无预防神经退行性变或诱导神经元修复的治疗方法。因此,对这两种疾病的新研究需求迫在眉睫。本文献综述旨在收集 PD 和 AD 的已发表研究,并探讨内源性大麻素系统 (ECS) 作为神经退行性变潜在药物靶点的当前应用。PD 常采用 L-DOPA 和深部脑刺激治疗。最近的基因修饰和重塑技术,如通过人类胚胎干细胞和诱导多能干细胞的 CRISPR,为个性化医疗展示了有前途的策略。AD 的特征是细胞外淀粉样β-老年斑和tau 蛋白神经原纤维缠结的沉积,通常采用胆碱乙酰转移酶增强剂作为治疗方法。ECS 目前正被作为 PD 和 AD 的药物靶点进行研究,其中 ECS 受体的过表达对 PD 具有神经保护作用,并减轻 AD 中的神经炎症。植物大麻中的大麻素 Δ-9-四氢大麻酚 (Δ-THC) 和大麻二酚 (CBD) 显示出对 PD 和 AD 动物模型的神经保护作用,但直接给药时会对患者产生毒性作用。因此,建议深入了解大麻素治疗后的精确分子级联反应,特别关注基因表达,以确定预防和修复神经退行性变的药物靶点。