SLC1A4 and Serine Homeostasis: Implications for Neurodevelopmental and Neurodegenerative Disorders

The solute carrier family 1 member 4 (SLC1A4) gene encodes a neutral amino acid transporter, also referred to as alanine-serine-cysteine transporter 1, ASCT1, that helps maintain amino acid balance in the brain and periphery. In the brain, SLC1A4 plays an important role in transporting levo (L) and dopa (D) isomers of serine. L-serine is required for many cellular processes, including protein and sphingolipid synthesis, while D-serine is a co-agonist required for normal neurotransmission through N-methyl-D-aspartate receptors. Through its roles transporting L-serine across the blood-brain barrier and regulating synaptic D-serine levels, SLC1A4 helps establish and maintain brain health across the lifespan. This review examines the role of SLC1A4 in neurodevelopment and neurodegeneration and assesses the therapeutic potential of serine supplementation to treat neurodevelopmental symptoms associated with mutations in SLC1A4, as well as schizophrenia, depression, traumatic brain injury, and Alzheimer's and Parkinson's diseases.