SLC1A4 and Serine Homeostasis: Implications for Neurodevelopmental and Neurodegenerative Disorders

Elazar, Dana; Alvarez, Natalie; Drobeck, Sabrina; Gunn, Teresa M.

doi:10.3390/ijms26052104

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SLC1A4 and Serine Homeostasis: Implications for Neurodevelopmental and Neurodegenerative Disorders

¹

Touro College of Osteopathic Medicine, Touro University, Great Falls, MT 59405, USA

²

McLaughlin Research Institute, Great Falls, MT 59405, USA

^*

Author to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

Int. J. Mol. Sci. 2025, 26(5), 2104; https://doi.org/10.3390/ijms26052104

Submission received: 28 January 2025 / Revised: 23 February 2025 / Accepted: 26 February 2025 / Published: 27 February 2025

(This article belongs to the Special Issue Neurodegenerative Disease: From Molecular Basis to Therapy, 3rd Edition)

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Abstract

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.

Keywords: solute carrier family 1 member 4 (SLC1A4) gene; SLC1A4; serine homeostasis; SPATCCM; neurodevelopment; neurodegeneration; Alzheimer’s disease

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MDPI and ACS Style

Elazar, D.; Alvarez, N.; Drobeck, S.; Gunn, T.M. SLC1A4 and Serine Homeostasis: Implications for Neurodevelopmental and Neurodegenerative Disorders. Int. J. Mol. Sci. 2025, 26, 2104. https://doi.org/10.3390/ijms26052104

AMA Style

Elazar D, Alvarez N, Drobeck S, Gunn TM. SLC1A4 and Serine Homeostasis: Implications for Neurodevelopmental and Neurodegenerative Disorders. International Journal of Molecular Sciences. 2025; 26(5):2104. https://doi.org/10.3390/ijms26052104

Chicago/Turabian Style

Elazar, Dana, Natalie Alvarez, Sabrina Drobeck, and Teresa M. Gunn. 2025. "SLC1A4 and Serine Homeostasis: Implications for Neurodevelopmental and Neurodegenerative Disorders" International Journal of Molecular Sciences 26, no. 5: 2104. https://doi.org/10.3390/ijms26052104

APA Style

Elazar, D., Alvarez, N., Drobeck, S., & Gunn, T. M. (2025). SLC1A4 and Serine Homeostasis: Implications for Neurodevelopmental and Neurodegenerative Disorders. International Journal of Molecular Sciences, 26(5), 2104. https://doi.org/10.3390/ijms26052104

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

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SLC1A4 and Serine Homeostasis: Implications for Neurodevelopmental and Neurodegenerative Disorders

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