线粒体疾病(MD)可能是由影响核或线粒体基因的突变引起的。编码线粒体蛋白,或非蛋白质编码线粒体RNA。尽管受影响的基因有很大的变异性,在最严重的情况下,观察到神经肌肉和神经退行性表型,并且没有特定的治疗方法可以从疾病中完全康复。最常用的治疗方法是对症治疗,并基于抗氧化剂鸡尾酒与抗癫痫/抗精神病药物的联合使用以及多器官受累的支持疗法。然而,抗氧化剂鸡尾酒疗法对患有MD的患者的真正效用仍需要科学证明。不幸的是,使用α-生育酚的抗氧化疗法的临床试验,抗坏血酸,谷胱甘肽,核黄素,烟酸,乙酰肉碱和辅酶Q取得了有限的成功。的确,预计使用的抗氧化剂只有在能够针对特定机制的情况下才能有效,即,涉及中枢和周围神经系统,负责疾病的临床表现。值得注意的是,通常,表征MD患者的表型与功能不依赖于特定辅因子的蛋白质突变有关。相反,抗氧化剂混合物的施用可能决定内源性氧化剂的抑制,导致对患者的细胞活力和/或毒性的有害影响。为了避免毒性作用,在施用抗氧化剂治疗之前,确定MD患者的血清抗氧化剂和辅因子水平可能很有用.检查影响蛋白质的突变的定位也是值得的,这些蛋白质的功能应该(更直接或更直接)依赖于待施用的辅因子。用于估计实际需求并预测拟议的基于辅因子/抗氧化剂的治疗的成功。
Mitochondrial diseases (MDs) may result from mutations affecting nuclear or mitochondrial genes, encoding mitochondrial proteins, or non-protein-coding mitochondrial RNA. Despite the great variability of affected genes, in the most severe cases, a neuromuscular and neurodegenerative phenotype is observed, and no specific therapy exists for a complete recovery from the disease. The most used treatments are symptomatic and based on the administration of antioxidant cocktails combined with antiepileptic/antipsychotic drugs and supportive therapy for multiorgan involvement. Nevertheless, the real utility of antioxidant cocktail treatments for patients affected by MDs still needs to be scientifically demonstrated. Unfortunately, clinical trials for antioxidant therapies using α-tocopherol, ascorbate, glutathione, riboflavin, niacin, acetyl-carnitine and coenzyme Q have met a limited success. Indeed, it would be expected that the employed antioxidants can only be effective if they are able to target the specific mechanism, i.e., involving the central and peripheral nervous system, responsible for the clinical manifestations of the disease. Noteworthily, very often the phenotypes characterizing MD patients are associated with mutations in proteins whose function does not depend on specific cofactors. Conversely, the administration of the antioxidant cocktails might determine the suppression of endogenous oxidants resulting in deleterious effects on cell viability and/or toxicity for patients. In order to avoid toxicity effects and before administering the antioxidant therapy, it might be useful to ascertain the blood serum levels of antioxidants and cofactors to be administered in MD patients. It would be also worthwhile to check the localization of mutations affecting proteins whose function should depend (less or more directly) on the cofactors to be administered, for estimating the real need and predicting the success of the proposed cofactor/antioxidant-based therapy.