Substantial evidence indicates bioenergetic dysfunction and mitochondrial impairment contribute either directly and/or indirectly to the pathogenesis of numerous neurodegenerative disorders. Treatment paradigms aimed at ameliorating this cellular energy deficit and/or improving mitochondrial function in these neurodegenerative disorders may prove to be useful as a therapeutic intervention. Creatine is a molecule that is produced both endogenously, and acquired exogenously through diet, and is an extremely important molecule that participates in buffering intracellular energy stores. Once creatine is transported into cells, creatine kinase catalyzes the reversible transphosphorylation of creatine via ATP to enhance the phosphocreatine energy pool. Creatine kinase enzymes are located at strategic intracellular sites to couple areas of high energy expenditure to the efficient regeneration of ATP. Thus, the creatine kinase/phosphocreatine system plays an integral role in energy buffering and overall cellular bioenergetics. Originally, exogenous creatine supplementation was widely used only as an ergogenic aid to increase the phosphocreatine pool within muscle to bolster athletic performance. However, the potential therapeutic value of creatine supplementation has recently been investigated with respect to various neurodegenerative disorders that have been associated with bioenergetic deficits as playing a role in disease etiology and/or progression which include; Alzheimer's, Parkinson's, amyotrophic lateral sclerosis (ALS), and Huntington's disease. This review discusses the contribution of mitochondria and bioenergetics to the progression of these neurodegenerative diseases and investigates the potential neuroprotective value of creatine supplementation in each of these neurological diseases. In summary, current literature suggests that exogenous creatine supplementation is most efficacious as a treatment paradigm in Huntington's and Parkinson's disease but appears to be less effective for ALS and Alzheimer's disease.

中文翻译：

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肌酸及其在神经退行性疾病中靶向细胞能量损伤的潜在治疗价值。

大量证据表明生物能功能障碍和线粒体损伤直接和/或间接导致了许多神经退行性疾病的发病机制。旨在改善这些神经退行性疾病中的这种细胞能量缺乏和/或改善线粒体功能的治疗范式可能被证明可用作治疗干预。肌酸是一种通过饮食内源性产生和外源性获得的分子，并且是参与缓冲细胞内能量储存的极其重要的分子。一旦肌酸被转运到细胞中，肌酸激酶就会通过 ATP 催化肌酸的可逆转磷酸化，以增强磷酸肌酸能量库。肌酸激酶位于重要的细胞内位点，将高能量消耗区域与 ATP 的有效再生结合起来。因此，肌酸激酶/磷酸肌酸系统在能量缓冲和整体细胞生物能量学中起着不可或缺的作用。最初，外源性肌酸补充剂仅被广泛用作增肌助剂，以增加肌肉内的磷酸肌酸库，以增强运动表现。然而，最近针对与生物能量缺陷相关的各种神经退行性疾病研究了肌酸补充剂的潜在治疗价值，这些疾病在疾病病因和/或进展中发挥作用，包括：阿尔茨海默病、帕金森病、肌萎缩侧索硬化症 (ALS) 和亨廷顿病。本综述讨论了线粒体和生物能量学对这些神经退行性疾病进展的贡献，并研究了肌酸补充剂在这些神经系统疾病中的潜在神经保护价值。总之，目前的文献表明，外源性肌酸补充剂作为亨廷顿氏症和帕金森氏病的治疗范例最有效，但似乎对 ALS 和阿尔茨海默氏病的疗效较差。