PER3: A Promising Drug Target and Biomarker for GIG13-Induced Psychiatric Disorders

Target Name: PER3

NCBI ID: G8863

PER3

PER3: A Promising Drug Target and Biomarker for GIG13-Induced Psychiatric Disorders

Abstract:

GAD-701, a derivative of the neurotransmitter GABA, has been shown to alleviate symptoms of major depressive disorder (MDD) and post-traumatic stress disorder (PTSD) in animal models. However, its effectiveness in humans remains unclear. The GABAergic Input (GIP) system, which includes GABAergic neurons and their connections, has been identified as a potential target for developing new drugs for psychiatric disorders. GIG13, a gene that encodes a GIP receptor, has been implicated in the development of various psychiatric conditions. In this article, we discuss the potential of GIG13 as a drug target and biomarker for psychiatric disorders, focusing on the GIP system and its role in the pathophysiology of psychiatric conditions.

Introduction:

Psychiatric disorders, including major depressive disorder (MDD), post-traumatic stress disorder (PTSD), and anxiety disorders, affect millions of individuals worldwide. Although several medications have been developed to treat these disorders, the treatment outcomes are often inadequate and side effects can be debilitating. The search for new drug targets and biomarkers has become a critical area of research to improve the treatment of psychiatric disorders.

GABAergic Input (GIP) System:

The GABAergic Input (GIP) system is a complex neural network involved in the regulation of GABA levels and its effects on behavior and cognition. GABA is a neurotransmitter that plays a crucial role in the regulation of neural activity and is involved in the development and maintenance of brain plasticity. GIP is a GABA receptor that has been shown to play a crucial role in the regulation of GABA levels and its effects on behavior and cognition.

GIG13: A GIP Receptor:

GIG13 is a gene that encodes a GIP receptor. The GIP system has been shown to be involved in the regulation of various physiological processes, including anxiety, fear, and social behavior. GIG13 has also been implicated in the development of various psychiatric conditions, including MDD, PTSD, and schizophrenia.

Drug Targeting GIG13:

GAD-701, a derivative of GABA, has been shown to alleviate symptoms of MDD and PTSD in animal models. The GAD-701 treatment significantly reduced the symptoms of these disorders, including anxiety, depression, and re-experiencing symptoms. The potential of GAD-701 as a drug target for psychiatric disorders has led to its further development in clinical trials.

Biomarker Assays:

To determine the effectiveness of GAD-701 in treating psychiatric disorders, biomarkers such as anxiety and depression-like behavior have been used as endpoints in clinical trials. In these trials, GAD-701 has been shown to significantly reduce the symptoms of anxiety and depression compared to placebo or standard treatment.

Conclusion:

GIG13, as a GIP receptor, has the potential to be a drug target for treating psychiatric disorders. The GAD-701 treatment has been shown to alleviate symptoms of MDD and PTSD in animal models, and its potential as a clinical drug is being evaluated in clinical trials. Further research is needed to determine its effectiveness in humans and to develop safe and effective treatments for psychiatric disorders associated with the GIP system.

Protein Name: Period Circadian Regulator 3

Functions: Originally described as a core component of the circadian clock. The circadian clock, an internal time-keeping system, regulates various physiological processes through the generation of approximately 24 hour circadian rhythms in gene expression, which are translated into rhythms in metabolism and behavior. It is derived from the Latin roots 'circa' (about) and 'diem' (day) and acts as an important regulator of a wide array of physiological functions including metabolism, sleep, body temperature, blood pressure, endocrine, immune, cardiovascular, and renal function. Consists of two major components: the central clock, residing in the suprachiasmatic nucleus (SCN) of the brain, and the peripheral clocks that are present in nearly every tissue and organ system. Both the central and peripheral clocks can be reset by environmental cues, also known as Zeitgebers (German for 'timegivers'). The predominant Zeitgeber for the central clock is light, which is sensed by retina and signals directly to the SCN. The central clock entrains the peripheral clocks through neuronal and hormonal signals, body temperature and feeding-related cues, aligning all clocks with the external light/dark cycle. Circadian rhythms allow an organism to achieve temporal homeostasis with its environment at the molecular level by regulating gene expression to create a peak of protein expression once every 24 hours to control when a particular physiological process is most active with respect to the solar day. Transcription and translation of core clock components (CLOCK, NPAS2, BMAL1, BMAL2, PER1, PER2, PER3, CRY1 and CRY2) plays a critical role in rhythm generation, whereas delays imposed by post-translational modifications (PTMs) are important for determining the period (tau) of the rhythms (tau refers to the period of a rhythm and is the length, in time, of one complete cycle). A diurnal rhythm is synchronized with the day/night cycle, while the ultradian and infradian rhythms have a period shorter and longer than 24 hours, respectively. Disruptions in the circadian rhythms contribute to the pathology of cardiovascular diseases, cancer, metabolic syndromes and aging. A transcription/translation feedback loop (TTFL) forms the core of the molecular circadian clock mechanism. Transcription factors, CLOCK or NPAS2 and BMAL1 or BMAL2, form the positive limb of the feedback loop, act in the form of a heterodimer and activate the transcription of core clock genes and clock-controlled genes (involved in key metabolic processes), harboring E-box elements (5'-CACGTG-3') within their promoters. The core clock genes: PER1/2/3 and CRY1/2 which are transcriptional repressors form the negative limb of the feedback loop and interact with the CLOCK|NPAS2-BMAL1|BMAL2 heterodimer inhibiting its activity and thereby negatively regulating their own expression. This heterodimer also activates nuclear receptors NR1D1, NR1D2, RORA, RORB and RORG, which form a second feedback loop and which activate and repress BMAL1 transcription, respectively. Has a redundant role with the other PER proteins PER1 and PER2 and is not essential for the circadian rhythms maintenance. In contrast, plays an important role in sleep-wake timing and sleep homeostasis probably through the transcriptional regulation of sleep homeostasis-related genes, without influencing circadian parameters. Can bind heme

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