Autophagy and amino acid metabolism in the brain: implications for epilepsy

Amino Acids. 2015 Oct;47(10):2113-26. doi: 10.1007/s00726-014-1822-z. Epub 2014 Aug 22.

Abstract

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.

Keywords: Epilepsy; Glutamine; Ketogenic diet; Leucine; Macroautophagy; mTOR.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amino Acids / metabolism*
  • Animals
  • Autophagy*
  • Brain / physiopathology*
  • Epilepsy / physiopathology*
  • Humans
  • Signal Transduction*

Substances

  • Amino Acids