Department of Health Biotechnology, EuroEspes Biotechnology, Corunna 15165, Spain.
EuroEspes Biomedical Research Center, Institute for CNS Disorders and Genomic Medicine, Corunna 15166, Spain.
Curr Neuropharmacol. 2019;17(3):295-306. doi: 10.2174/1570159X17666181127125704.
The research progress of understanding the etiology and pathogenesis of Parkinson's disease (PD) has yet lead to the development of some clinical approaches intended to treat cognitive and behavioral symptoms, such as memory and perception disorders. Despite the major advances in different genetic causes and risk factors for PD, which share common pathways to cell dysfunction and death, there is not yet a complete model of PD that can be used to accurately predict the effect of drugs on disease progression. Clinical trials are also important to test any novel neuro-protective agent, and recently there have been great advances in the use of anti-inflammatory drugs and plant flavonoid antioxidants to protect against specific neuronal degeneration and its interference with lipid and cholesterol metabolism. The increasing knowledge of the molecular events underlying the degenerative process of PD has stimulated research to identify natural compounds capable of halting or slowing the progress of neural deterioration. Polyphenols and flavonoids, which play a neuroprotective role in a wide array of in vitro and in vivo models of neurological disorders, emerged from among the multi-target bio-agents found mainly in plants and microorganisms. This review presents a detailed overview of the multimodal activities of neuroprotective bio-agents tested so far, emphasizing their neurorescue/neuroregenerative activity. The brain-penetrating property of bioagents may make these compounds an important class of natural drugs for the treatment of neurodegenerative diseases. Although there are numerous studies demonstrating beneficial effects in the laboratory by identifying critical molecular targets, the clinical efficacy of these neuroprotective treatments remains to be proven accurately.
目前,对于帕金森病(PD)的病因和发病机制的研究进展尚未导致一些旨在治疗认知和行为症状(如记忆和感知障碍)的临床方法的发展。尽管在不同的 PD 遗传原因和风险因素方面取得了重大进展,这些因素具有共同的细胞功能障碍和死亡途径,但仍没有一个完整的 PD 模型可以准确预测药物对疾病进展的影响。临床试验对于测试任何新型神经保护剂也很重要,最近,使用抗炎药物和植物类黄酮抗氧化剂来预防特定神经元变性及其对脂质和胆固醇代谢的干扰方面取得了重大进展。对 PD 退行性过程中分子事件的日益了解,刺激了研究识别能够阻止或减缓神经恶化的天然化合物。多酚和类黄酮在广泛的体外和体内神经紊乱模型中发挥神经保护作用,它们是从主要存在于植物和微生物中的多靶点生物制剂中筛选出来的。本文详细综述了迄今为止测试的神经保护生物制剂的多模式活性,强调了它们的神经挽救/神经再生活性。生物制剂的脑穿透特性可能使这些化合物成为治疗神经退行性疾病的一类重要天然药物。尽管有许多研究通过确定关键的分子靶点在实验室中证明了这些神经保护治疗的有益效果,但这些治疗的临床疗效仍有待准确证明。