GPR88

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GPR88 is a G protein-coupled receptor encoded by the GPR88 gene in humans. This receptor is predominantly expressed in the brain, with high levels in the striatum, a brain region involved in the coordination of movement, as well as in various aspects of cognition including decision-making, motivation, reinforcement, and reward perception. The exact physiological role of GPR88 is still under investigation, but it is thought to play a critical role in the regulation of dopamine signaling pathways, which are crucial for normal brain function and have been implicated in numerous neurological and psychiatric disorders.

Function[edit | edit source]

GPR88 is an orphan receptor, meaning its endogenous ligand (naturally occurring molecule that binds to the receptor) has not been identified. Despite this, research has shown that GPR88 plays a significant role in the central nervous system. It modulates several key brain functions, including motor activity, emotional responses, and cognitive processes. Animal studies have suggested that alterations in GPR88 expression or function can lead to behavioral changes, including increased anxiety-like behavior, altered response to psychostimulants, and deficits in motor coordination and learning.

Clinical Significance[edit | edit source]

Given its prominent expression in the striatum and its involvement in dopamine signaling, GPR88 is of significant interest in the study of psychiatric and neurological disorders, such as schizophrenia, Parkinson's disease, and addiction. Abnormal GPR88 function or expression levels may contribute to the pathophysiology of these conditions. Consequently, GPR88 is being explored as a potential therapeutic target. Modulating GPR88 activity could offer new avenues for the treatment of disorders associated with dopaminergic dysfunction.

Research Directions[edit | edit source]

Current research on GPR88 is focused on identifying its endogenous ligand, understanding its signaling pathways, and elucidating its role in the brain. Additionally, the development of small molecule modulators of GPR88 could provide tools for further research and potential therapeutic compounds. Animal models, particularly genetically modified mice lacking the GPR88 gene, have been invaluable in uncovering the functions and potential clinical relevance of this receptor.

Conclusion[edit | edit source]

GPR88 represents a promising area of research with potential implications for understanding and treating a variety of brain disorders. Its role in modulating dopamine signaling pathways makes it a particularly intriguing target for therapeutic intervention in conditions characterized by dopaminergic dysregulation.


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Contributors: Prab R. Tumpati, MD