Ferreira Gustavo C, McKenna Mary C
Institute of Medical Biochemistry Leopoldo de Meis, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
Department of Pediatrics, University of Maryland School of Medicine, 655 W. Baltimore Street, BRB 13-019, Baltimore, MD, 21201, USA.
Neurochem Res. 2017 Jun;42(6):1661-1675. doi: 10.1007/s11064-017-2288-7. Epub 2017 May 16.
L-Carnitine functions to transport long chain fatty acyl-CoAs into the mitochondria for degradation by β-oxidation. Treatment with L-carnitine can ameliorate metabolic imbalances in many inborn errors of metabolism. In recent years there has been considerable interest in the therapeutic potential of L-carnitine and its acetylated derivative acetyl-L-carnitine (ALCAR) for neuroprotection in a number of disorders including hypoxia-ischemia, traumatic brain injury, Alzheimer's disease and in conditions leading to central or peripheral nervous system injury. There is compelling evidence from preclinical studies that L-carnitine and ALCAR can improve energy status, decrease oxidative stress and prevent subsequent cell death in models of adult, neonatal and pediatric brain injury. ALCAR can provide an acetyl moiety that can be oxidized for energy, used as a precursor for acetylcholine, or incorporated into glutamate, glutamine and GABA, or into lipids for myelination and cell growth. Administration of ALCAR after brain injury in rat pups improved long-term functional outcomes, including memory. Additional studies are needed to better explore the potential of L-carnitine and ALCAR for protection of developing brain as there is an urgent need for therapies that can improve outcome after neonatal and pediatric brain injury.
左旋肉碱的作用是将长链脂肪酰辅酶A转运至线粒体，通过β-氧化进行降解。用左旋肉碱治疗可改善许多先天性代谢缺陷中的代谢失衡。近年来，左旋肉碱及其乙酰化衍生物乙酰左旋肉碱（ALCAR）在多种疾病（包括缺氧缺血、创伤性脑损伤、阿尔茨海默病以及导致中枢或外周神经系统损伤的情况）中的神经保护治疗潜力引起了广泛关注。临床前研究有令人信服的证据表明，在成人、新生儿和小儿脑损伤模型中，左旋肉碱和ALCAR可改善能量状态、降低氧化应激并预防随后的细胞死亡。ALCAR可提供一个可被氧化以供能的乙酰基团，用作乙酰胆碱的前体，或并入谷氨酸、谷氨酰胺和γ-氨基丁酸，或并入脂质以用于髓鞘形成和细胞生长。在幼鼠脑损伤后给予ALCAR可改善长期功能结局，包括记忆。由于迫切需要能够改善新生儿和小儿脑损伤后结局的治疗方法，因此需要进行更多研究以更好地探索左旋肉碱和ALCAR对发育中大脑的保护潜力。
