Unitat de Farmacología, Centros de Investigación Biomédica en Red de Enfermedades Neurodegenerativas, Facultat de Medicina i Ciències de la Salut, Universitat Rovira i Virgili, Reus, Tarragona, Spain.
Curr Pharm Des. 2011;17(3):230-45. doi: 10.2174/138161211795049732.
The purpose of this review is to discuss potential pathways involved in the pathogenesis of neurodegenerative diseases, highlighting current pharmacological drug targets in neuronal apoptosis prevention. The incidence of these disorders is expected to rise in the coming years and so finding effective treatments represents a significant challenge for medicine. Alzheimer's disease and Parkinson's disease were both described almost a century ago and are the most important neurodegenerative disorders in the developed world. However, the molecular mechanisms that lead to the development of the neuronal pathology in both diseases are unclear. For this reason, despite substantial research in the area, an effective treatment for these diseases does not yet exist. In the present study we discuss in depth the pathways involved in apoptosis and neuronal death in neurodegenerative diseases. We also examine drugs that may have a neuroprotective effect. Inhibition of apoptosis mediated by oxidative stress generation and mitochondrial alteration or by the blockade of NMDA receptors could constitute a suitable therapeutic strategy for Alzheimer's disease. A multiple therapy with antioxidants, cell cycle inhibitors, GSK3β inhibitors, and STATINS could, in the future, represent a suitable strategy for delaying the progression of neurodegenerative diseases. This research contributes to the development of new methods in the field of apoptosis inhibitors that could provide the future tools for the treatment of Alzheimer's and Parkinson's disease, as well as other neurodegenerative diseases.
本文的目的在于讨论神经退行性疾病发病机制中涉及的潜在途径，重点阐述神经元凋亡预防的当前药理学药物靶点。预计这些疾病的发病率在未来几年将会上升，因此寻找有效的治疗方法是医学面临的一项重大挑战。阿尔茨海默病和帕金森病都在近一个世纪前被描述过，是发达国家最重要的神经退行性疾病。然而，导致这两种疾病神经元病理发展的分子机制尚不清楚。因此，尽管在该领域进行了大量研究，但这些疾病仍然没有有效的治疗方法。在本研究中，我们深入探讨了神经退行性疾病中细胞凋亡和神经元死亡的相关途径。我们还研究了可能具有神经保护作用的药物。抑制由氧化应激产生和线粒体改变介导的细胞凋亡，或阻断 NMDA 受体，可能构成阿尔茨海默病的一种合适的治疗策略。未来，用抗氧化剂、细胞周期抑制剂、GSK3β 抑制剂和他汀类药物进行多种联合治疗，可能代表一种延缓神经退行性疾病进展的合适策略。这项研究有助于开发细胞凋亡抑制剂领域的新方法，为阿尔茨海默病和帕金森病以及其他神经退行性疾病的治疗提供未来的工具。
