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Study sheds new light on proteins and its efficacy on psychotropic drugs

CUIMC researchers made a new discovery that may help improve future psychiatric treatment.

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Researchers have made a new discovery that could make future psychopharmacological treatments more efficient for mood and behavior disorders.

In a study, conducted at Columbia University Irving Medical Center (CUIMC), researchers investigated the role of particular transport proteins and how they work at a molecular level affecting the function of psychotropic drugs.

Neurotransmitter:sodium symporters (NSSs), a key focus of the study, are responsible for the release and re-uptake of neurotransmitters at the synapses. NSSs are the molecular target of numerous psychotropic treatments, including SSRI antidepressants.

Due to its role at the synapses, understanding the function of NSS is crucial for the development of better therapeutic drugs utilized in the treatment of depressive and anxiety disorders, researchers believe. In prior studies, the team of researchers focused on a bacterial form of NSS LeuT. They found a second substrate binding site also able to bind drugs.

In the new study, a different form was investigated: bacterial NSS homolog (MhsT). This bacterial form is more relatable to its human counterparts, based on the findings. The discovery of a second substrate binding site in this NSS suggests that the same mechanism could also be found in human NSS.

“Here, we provide evidence that MhsT, another NSS homolog, can simultaneously bind substrate molecules both in its primary substrate (S1) site and in its secondary substrate (S2) site,” the study reads.

“These data suggest that the involvement of two binding sites in neurotransmitter transport is not unique to LeuT but shared by other NSS members, and is possibly a universal feature of these many transport proteins,” said Jonathan Javitch, one of the lead researchers.

While neurotransmitter:sodium symporters remain a difficult subject, the findings could pave the way for sharper research in future studies.

“Looking forward, incorporating the knowledge from this new discovery into future NSS research could lead to better-informed therapeutics research and design, ultimately improving the lives of the millions of Americans afflicted with psychiatric disorders.”

The findings were published in the journal Proceedings of the National Academy of Sciences of the United States (PNAS).

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