Kumari Namrata, Daram Nagarjuna, Alam Md Sabir, Verma Anita Kamra
Institute of Molecular Medicine, Jamia Hamdard, Delhi, India.
Department of Biotechnology, Indian Institute of Technology, Roorkee, India.
CNS Neurol Disord Drug Targets. 2022;21(10):966-976. doi: 10.2174/1871527321666220512153854.
Neurodegenerative diseases are a heterogeneous group of disorders among aging populations worldwide characterized by the progressive degeneration of the structure and function of brain cells and the nervous system. Alzheimer's disease and Parkinson's disease are common neurodegenerative diseases (NDs). Classic pathological features of AD are the accumulation of the amyloid betaprotein and aggregates of hyperphosphorylated tau protein around the brain cells. Dopaminergic neuronal death in the midbrain and accumulation of α- synuclein in the neurons are the hallmark of Parkinson's disease. The pathogenesis is multifactorial, and both neurodegenerative disorders have complex etiology. Oxidative stress closely linked with mitochondrial dysfunction, excitotoxicity, nitric oxide toxicity, and neuro-inflammation, is anticipated to trigger neuronal death. Ample evidence has implicated that oxidative stress and inflammation contribute to the pathology of neurodegeneration in AD and PD. Currently, acetylcholinesterase inhibitors are the main treatment option for AD, while L-DOPA is the gold standard therapy for PD. Along with the main therapy, many endogenous antioxidants, like vitamin E, selenium, etc., are also given to the patients to combat oxidative stress. Current treatment for these NDs is limited due to the blood-brain barrier (BBB) that hinders drug targeting towards neurons. In this review, we emphasize adjunct treatment with anti-inflammatory agents that act at the site of the disease and can halt the disease progression by attenuating the effect of ROS triggering neuro-inflammatory response. Polyphenols, either as purified compounds or extracts from various natural plant sources, have been well studied and documented for anti-inflammatory effects, but their use for ND is limited due to their physicochemical attributes. Nanoparticle-mediated drug delivery system exhibits immense potential to overcome these hurdles in drug delivery to the CNS, enabling nanoparticle-based therapies to directly target the inflammation and release bioactive compounds with anti-inflammatory properties to the site of action.
神经退行性疾病是全球老年人群中一组异质性疾病，其特征是脑细胞和神经系统的结构与功能进行性退化。阿尔茨海默病和帕金森病是常见的神经退行性疾病。阿尔茨海默病的典型病理特征是淀粉样β蛋白的积累以及脑细胞周围过度磷酸化tau蛋白的聚集。中脑多巴胺能神经元死亡以及神经元中α-突触核蛋白的积累是帕金森病的标志。其发病机制是多因素的，这两种神经退行性疾病都有复杂的病因。与线粒体功能障碍、兴奋性毒性、一氧化氮毒性和神经炎症密切相关的氧化应激预计会引发神经元死亡。大量证据表明，氧化应激和炎症促成了阿尔茨海默病和帕金森病中神经退行性变的病理过程。目前，乙酰胆碱酯酶抑制剂是治疗阿尔茨海默病的主要选择，而左旋多巴是治疗帕金森病的金标准疗法。除了主要治疗方法外，还会给患者使用许多内源性抗氧化剂，如维生素E、硒等，以对抗氧化应激。由于血脑屏障阻碍药物靶向神经元，目前对这些神经退行性疾病的治疗有限。在这篇综述中，我们强调使用抗炎药物进行辅助治疗，这些药物作用于疾病部位，可通过减弱引发神经炎症反应的活性氧的作用来阻止疾病进展。多酚类物质，无论是作为纯化化合物还是从各种天然植物来源提取的提取物，其抗炎作用都已得到充分研究和记录，但由于其物理化学特性，它们在神经退行性疾病中的应用有限。纳米颗粒介导的药物递送系统在克服向中枢神经系统递送药物的这些障碍方面显示出巨大潜力，使基于纳米颗粒的疗法能够直接靶向炎症部位，并将具有抗炎特性的生物活性化合物释放到作用部位。
