Department of Psycho-Neurosciences and Rehabilitation, Faculty of Medicine and Pharmacy, University of Oradea, 410073 Oradea, Romania.
Neurology Ward, Clinical Municipal Hospital "dr. G. Curteanu" Oradea, 410154 Oradea, Romania.
Int J Mol Sci. 2021 Oct 31;22(21):11847. doi: 10.3390/ijms222111847.
As the population ages, the incidence of neurodegenerative diseases is increasing. Due to intensive research, important steps in the elucidation of pathogenetic cascades have been made and significantly implicated mitochondrial dysfunction and oxidative stress. However, the available treatment in Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis is mainly symptomatic, providing minor benefits and, at most, slowing down the progression of the disease. Although in preclinical setting, drugs targeting mitochondrial dysfunction and oxidative stress yielded encouraging results, clinical trials failed or had inconclusive results. It is likely that by the time of clinical diagnosis, the pathogenetic cascades are full-blown and significant numbers of neurons have already degenerated, making it impossible for mitochondria-targeted or antioxidant molecules to stop or reverse the process. Until further research will provide more efficient molecules, a healthy lifestyle, with plenty of dietary antioxidants and avoidance of exogenous oxidants may postpone the onset of neurodegeneration, while familial cases may benefit from genetic testing and aggressive therapy started in the preclinical stage.
随着人口老龄化,神经退行性疾病的发病率正在增加。由于深入的研究,在阐明发病机制方面已经取得了重要进展,并显著表明线粒体功能障碍和氧化应激的作用。然而,目前针对阿尔茨海默病、帕金森病和肌萎缩侧索硬化症的治疗主要是对症治疗,只能带来微小的益处,最多只能减缓疾病的进展。尽管在临床前研究中,针对线粒体功能障碍和氧化应激的药物取得了令人鼓舞的结果,但临床试验却失败或结果不确定。很可能在临床诊断时,发病机制已经全面展开,大量神经元已经退化,使得针对线粒体的药物或抗氧化分子无法阻止或逆转这一过程。在进一步的研究提供更有效的分子之前,健康的生活方式,摄入充足的膳食抗氧化剂和避免外源性氧化剂,可能会推迟神经退行性变的发生,而对于家族性病例,可能会受益于遗传检测和在临床前阶段开始的积极治疗。