Beyond Nutrition: Deciphering the Roles of Amino Acids as Molecular Regulators of Memory Mechanisms

Abstract

Memory formation is a complex process involving multiple neural and molecular mechanisms through synaptic plasticity, neurotransmission, and intracellular signaling pathways. While these processes are nutrient-sensitive, the specific mechanistic roles of dietary amino acids in memory pathways remain underexplored. This review analyzes evidence on how key amino acids (e.g. glutamate, tryptophan, and BCAAs) regulate molecular mechanisms of memory. Glutamate drives long-term potentiation (LTP) through NMDAR and mGLUR activation, although its activity requires tight regulation to avoid excitotoxicity. Tryptophan availability enhances serotonergic signaling, promoting LTP and memory consolidation through PKA/CREB and MAPK signaling pathways. Branched-chain amino acids (BCAAs) and large neutral amino acids (LNAAs) modulate central neurotransmitter synthesis through competitive transport at the blood-brain barrier, thereby influencing synaptic signaling. Additionally, amino acids availability regulates epigenetic processes via methyl donor metabolism and acetyl-CoA production, mechanisms that are closely linked to activity-dependent gene expression underlying synaptic plasticity and memory function. Amino acid modulates memory formation through molecular mechanisms in synaptic plasticity, neurotransmitters, and intracellular signaling pathways. Targeting amino acids intake offers promising strategies for cognitive health. Future research should prioritize human studies, personalized nutrition, and gut microbiome-amino acids interactions.

Keywords: amino acids, memory formation, neurotransmitters, synaptic plasticity