Adhihetty Peter J, Beal M Flint
Department of Neurology and Neuroscience, Weill Medical College of Cornell University, 525 East 68th Street, New York, NY 10021, USA.
Neuromolecular Med. 2008;10(4):275-90. doi: 10.1007/s12017-008-8053-y. Epub 2008 Nov 13.
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.
大量证据表明，生物能量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细胞能量不足和/或改善线粒体功能的治疗模式可能被证明是一种有用的治疗干预措施。肌酸是一种内源性产生且可通过饮食外源性获取的分子，是参与缓冲细胞内能量储备的极其重要的分子。一旦肌酸被转运到细胞中，肌酸激酶通过ATP催化肌酸的可逆转磷酸化，以增强磷酸肌酸能量池。肌酸激酶位于细胞内的关键位置，将高能量消耗区域与ATP的高效再生相耦合。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，外源性补充肌酸仅被广泛用作一种提高肌肉内磷酸肌酸池以增强运动表现的促力剂。然而，最近已经针对各种与生物能量缺陷相关的神经退行性疾病研究了补充肌酸的潜在治疗价值，这些疾病在疾病病因和/或进展中起作用，包括阿尔茨海默病、帕金森病、肌萎缩侧索硬化症（ALS）和亨廷顿舞蹈症。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，并研究了补充肌酸在每种神经疾病中的潜在神经保护价值。总之，目前的文献表明，外源性补充肌酸作为一种治疗模式在亨廷顿舞蹈症和帕金森病中最有效，但对ALS和阿尔茨海默病似乎效果较差。
