To date, glycogen synthase kinase (GSK3) has been shown to regulate more than 100 proteins by phosphorylating a serine or threonine residue on its target substrate, with a growing number identified as having roles in neurobiological processes. The inhibition of GSK3 is regarded as an important role in psychotropic drug development. With professional experience accumulated from hundreds of projects, Creative Biolabs is capable of providing detailed target development services to global researchers.
Introduction to GSK3
The serine/threonine kinase GSK-3, which was originally discovered to phosphorylate and thus inactivate glycogen synthesis, is now known for involving in a variety of cellular processes including cell proliferation, cell survival, apoptosis, and inflammation. There are two GSK-3 isoforms (GSK-3α and GSK-3β) that are encoded by different genes but share significant similarities in their primary sequences. Both isoforms are present in most cells and tissues including the brain and specifically in neurons, astrocytes, and microglia. Studies using rodent brain tissue have demonstrated that GSK-3β is particularly abundant in the hippocampus and neocortex.
GSK-3 Inhibitors as Therapeutic Agents in Neuropsychiatric Disorders
The actions of GSK3 are involved in the pathophysiology of bipolar mood disorder. This evidence stems from the inhibitory actions on GSK3 of therapeutic interventions used in this illness. Either GSK3 itself or signaling intermediates coupled to GSK3 may be abnormal in bipolar disorder, so inhibition of GSK3 may contribute to normalizing these targets. Dysfunctional GSK3, or molecules linked to GSK3, also may contribute to major depression. The most prevalent model for the pathological cause of depression is the monoamine hypothesis, which suggests that depression stems from inadequate serotonin (5HT) and/or norepinephrine neurotransmission. Research on 5HT receptor signaling and GSK3β suggests that 5HT receptor actions, especially the balance of activities between 5HT1A and 5HT2 receptor subtypes, can regulate GSK3β in the brain. Abnormally active GSK3 due to 5HT receptor signaling dysfunction could contribute to the pathophysiology of depression and that a part of the therapeutic effects of increased serotonergic activity by antidepressants is mediated by GSK3 inhibition.
It is now well-established that GSK-3 modulates the accumulation of amyloid-β (Aβ) and modifies tau, the main components of senile plaques and neurofibrillary tangles, respectively, which are pathophysiological hallmarks of AD. As such, much effort has been focused on determining whether GSK-3 inhibitors can improve cognitive functioning in AD and attenuate its associated pathophysiology. Preclinical studies using animal models of AD strongly support the hypothesis that inhibition of GSK-3β improves cognitive functioning and attenuates AD-associated pathologies, and thus might be a rational approach in the treatment of cognitive impairments in AD as well as other brain disorders.
Services at Creative Biolabs
Having been focusing on psychotropic drug development for years, Creative Biolabs has accumulated extensive experience in this field. Our mature drug development system, advanced technology platform, and professional scientists will assure the high quality of the services covering target discovery, biomarker development, preclinical model, validation, qualification, and so on. We provide both single-alone services and integrated projects depending on customers' choices.
According to enormous researches, GSK3 inhibitors have huge potential in psychotropic drug development. Creative Biolabs is committed to novel psychotropic target discovery and subsequent target development. We aim to promote industry development through our customer-satisfied services. If the above services do not meet your requirements, please feel free to contact us for more information.
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