Bejarano Eloy, Rodríguez-Navarro José Antonio
Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Chanin Building Room 502, 1300 Morris Park Avenue, Bronx, NY, 10461, USA.
Servicio de Neurobiología, Departamento de Investigación, Hospital Ramón y Cajal, Instituto Ramon y Cajal de Investigaciones Sanitarias, Carretera de Colmenar, km 9,100, Madrid, Spain.
Amino Acids. 2015 Oct;47(10):2113-26. doi: 10.1007/s00726-014-1822-z. Epub 2014 Aug 22.
Autophagy is a catabolic pathway responsible for the maintenance of the tissue and organism homeostasis. Several amino acids regulate autophagic activity in different tissues, such as liver and muscle, but much less is known about this regulation in the brain. The lack of autophagy in neurons leads to a strong neurodegenerative phenotype and epileptic disorders. We summarize the current knowledge about the regulation of autophagy mediated by amino acids and how macroautophagy could serve as source of amino acids. We review the contribution of macroautophagy in the brain physiology and pathology emphasizing the relevancy of the proper control of amino acid levels such as glutamate and GABA in the brain due to its role as neurotransmitters and energy source. Furthermore, we discuss how malfunction in autophagy may result in pathological consequences, because many genetic epileptic disorders are related to signaling or metabolic pathways controlling both macroautophagy and amino acid metabolism in the brain.
自噬是一种分解代谢途径,负责维持组织和机体的稳态。几种氨基酸可调节不同组织(如肝脏和肌肉)中的自噬活性,但关于大脑中这种调节的了解却少得多。神经元中自噬的缺失会导致强烈的神经退行性表型和癫痫疾病。我们总结了目前关于氨基酸介导的自噬调节以及巨自噬如何作为氨基酸来源的知识。我们回顾了巨自噬在大脑生理和病理中的作用,强调了适当控制大脑中谷氨酸和γ-氨基丁酸等氨基酸水平的相关性,因为它们作为神经递质和能量来源发挥作用。此外,我们讨论了自噬功能障碍如何导致病理后果,因为许多遗传性癫痫疾病与控制大脑中巨自噬和氨基酸代谢的信号或代谢途径有关。