Amino Acid That Delivers Slow Down Signal to Brain Linked to Major Depression


The amino acid glycine is crucial in the brain, operating as a neurotransmitter with both excitatory and inhibitory effects. This dual nature makes glycine and its receptors important targets for understanding and treating major depression. Recent findings by researchers at the Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology illustrate the role that glycine plays in delivering a “slow-down” signal to the brain. This action is thought to contribute to mood disorders like major depression and anxiety.

GPR158: A Potential Therapeutic Target

The research led by neuroscientist Kirill Martemyanov sheds light on the receptor GPR158, which was previously considered an orphan receptor. Orphan receptors are those that have no known ligands. However, the Martemyanov team found that GPR158 is sensitive to glycine, a simple amino acid found throughout mammalian tissues.

The discovery process involved detailed studies aimed at understanding how sensors on brain cells receive and send signals. This understanding is not only crucial for grasping how moods are regulated but also opens the door for creating new, faster-acting depression medications.

Glycine and Its Role in Depression

Glycine plays a pivotal role as a neurotransmitter with complex effects on the brain’s neural circuits. It can act both as an inhibitory and excitatory neurotransmitter, depending on the type of cell. This versatility means that glycine has the potential to modulate various brain functions, from memory to pain, and importantly, mood regulation.

Table: Effects of Glycine

Cell Type Action Example
Inhibitory Neurons Slow-down signal Reduced anxiety
Excitatory Neurons Stimulating signal Enhanced memory function
Prostate Cells Promotes growth Linked to prostate cancer

G Protein-Coupled Receptors (GPCRs)

GPCRs, like GPR158, are essential for neuronal function and pathology. They represent prime targets for drug development. Many orphan GPCRs still lack identified endogenous ligands. By solving the structure of GPR158, the team discovered that it acts more like bacterial receptors than human ones, leading them to hypothesize an amino acid ligand. This hypothesis was confirmed when glycine was found to fit perfectly, making GPR158 a newly identified receptor, mGlyR.

Chronic Stress and Depression

Chronic stress is a well-known factor in depression. Martemyanov’s previous studies showed that mice lacking the GPR158 gene displayed resilience to chronic stress. This indicated GPR158 as a promising target for antidepressant therapy. The newly solved structure of GPR158 shows that when glycine binds to this receptor, it triggers a braking mechanism in the cell.

List: GPR158 and its Functions

  • Acts as a receptor for glycine.
  • Inhibits cell activity upon glycine binding.
  • Plays a role in stress resilience.
  • Identified as mGlyR (metabotropic glycine receptor).

Impact on Treatment

The discovery of GPR158’s role as a glycine receptor could have significant implications for developing new treatments for depression. Many current depression medications are slow to take effect, often taking weeks to show benefits. New treatments targeting mGlyR could potentially offer faster relief, addressing a critical need in mental health care.

Economic and Social Implications

Depression is a major health concern with substantial social and economic impacts. According to the U.S. Centers for Disease Control and Prevention, the economic burden of depression in 2021 was $326 billion annually in the U.S alone. Numbers of affected people, especially young adults, have surged in recent years. The financial strain includes costs related to disability, medical care, and lost productivity.

Future Directions

Future research will need to explore how the body maintains the right balance of mGlyR receptors and how brain cell activity is affected. This understanding is crucial for creating effective, targeted treatments. Martemyanov and his team continue to investigate these pathways, aiming to leverage their findings for therapeutic advancements.

Key Researchers Involved

  • Kirill Martemyanov
  • Thibaut Laboute
  • Stefano Zucca
  • Stefano Forli
  • Matthew Holcomb
  • Chris Garza

Table: Key Components and Impact

Component Impact Details
Glycine Neurotransmitter Inhibitory and excitatory effects
GPR158 Receptor for glycine Inhibits cell activity, potential drug target
mGlyR Newly identified as GPR158 receptor Opportunities for new depression treatments
Chronic Stress Factor in depression GPR158 knockout mice show stress resilience
Economic Burden $326 billion annually in U.S Costs related to medical care, disability, lost productivity
Research Entities Collaborative efforts Wertheim UF Scripps Institute, National Institute of Health

New Therapies on the Horizon

The identification of mGlyR as a receptor impacted by glycine lays the groundwork for developing new depression treatments. Given the urgent need for faster-acting antidepressants, this finding is significant. Current medications have limitations, often taking weeks to become effective, which can be critical for patients in immediate distress.

Glycine’s Broader Impact

Glycine’s role in the body extends beyond mood regulation. It’s implicated in various physiological processes, sometimes sending slow-down signals, other times excitatory ones. More research will elucidate its full range of action, from support in brain functions to potential implications in cancer growth.


Martemyanov’s work unlocks new paths for treating mood-related disorders. By understanding how glycine interacts with brain cell receptors like GPR158, researchers can target these pathways for therapeutic purposes. The move from basic science to application is often lengthy, but findings like these set the stage for important advancements in mental health treatments.

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