GSK3b inhibition is one my favorite pathways for enhancement.
- Introduction to GSK3B
- Benefits to GSK3B Inhibition
- Genetics and GSK3B
- Top GSK3 beta Inhibitors
- What Increases GSK3b
Introduction to GSK3B
GSK3B (Glycogen synthase kinase 3 beta) is an enzyme associated with energy metabolism, neuronal cell development, and body pattern formation [R].
Glycogen synthase kinase 3 (GSK-3) is an essential “brake” on many growth-signaling pathways including Wnt and insulin. GSK-3 has high activity in resting tissues and is inhibited upon cellular stimulation [R].
Benefits to GSK3B Inhibition
2) Obesity and Type 2 Diabetes
Glycogen synthase kinase-3 (GSK-3) has important roles in the regulation of glycogen synthesis, protein synthesis, gene transcription, and cell differentiation in various cell types [R].
Inhibitors of GSK3 have been demonstrated to have anti-diabetic effects in test tubes and animal models [R]
Overexpression and overactivity of GSK-3 in the muscle of rodent models of obesity and type 2 diabetic humans are associated with an impaired ability of insulin to activate glucose disposal and glycogen synthase [R].
In muscle, GSK3b inhibits glycogen synthesis. [R]
GSK3B promotes ovarian cancer cell proliferation and chemotherapy resistance [R].
Pancreatic cancer cells contain a pool of active GSK3B, and inhibition of GSK3B leads to decreased cancer cell proliferation and survival [R].
Colon cancer cell from patients have higher levels of GSK3B expression than their normal counterparts [R].
4) Mood: Depression and Anxiety
Elderly depressed patients had significantly higher GSK3B activity. Higher GSK3B activity were observed in patients with severe depressive episode and with cognitive impairment [R].
5) Inflammation and Pain
GSK3-β induces TLR-mediated excessive inflammatory responses in the gut [R].
Blockade of GSK3-β attenuates excessive proinflammatory TLR-mediated immune responses. GSK3-β inhibition therefore constitutes a promising therapeutic option for selectively reducing exaggerated intestinal immune reactions toward the luminal flora in inflammatory bowel disease [R].
Inhibitors of GSK3b stop neuroinflammation and pain [R].
Inhibition of GSK3β in cells leads to suppression of Toll-like receptor (TLR)-initiated proinflammatory cytokines from NfkB.
GSK3b increases NfkB [R].
6) Sociability and Resilience
GSK3 inhibition (hippocampus and striatum) increases resilience to defeat and decreases responsiveness to psychostimulants [R].
7) Nootropic Effects
GSK3 is critical for brain development and neuroplasticity, which appear to be interrelated and to mediate age-associated neurological diseases [R].
Specifically, GSK3 plays a pivotal role in controlling neuronal progenitor proliferation and establishment of neuronal polarity during development, and neuronal GSK3 function affect neuroplasticity throughout the lifespan [R].
GSK3 is proposed to be a therapeutic target for restoration of synaptic functioning and cognition [R].
GSK3β inhibition stimulates the regeneration of myelin forming cells and remyelination following chemically induced demyelination [R].
GSK3b inhibition stimulates axon regeneration in injured cortical connections [R].
Damaged axons in the adult central nervous system normally do not regenerate after lesion, largely because of the presence of growth inhibitory molecules at the scar [R].
Glycogen synthase kinase-3 inhibitors reverse deficits in long-term potentiation and cognition in fragile X mice [R].
Mice injected with cocaine (20 mg/kg, i.p) showed an increase in the activity of GSK3β in the caudate putamen.
GSK3b inhibitors produced significant dose-dependent reductions in cocaine-induced activity (R).
GSK3 activity status is regulated by the circadian clock and GSK3 feeds back to regulate the molecular clock amplitude in the Supra Chiasmatic Nucleus [R].
Glycogen synthase kinase 3 (GSK3) interacts with at least 5 core clock proteins and shows daily variation itself. Significant circadian rhythmicity of phosphorylated GSK3 (α and β) was observed in the SCN [R].
GSK3b increases Rev-erb-a, while helping to break down ARNTL/BMAL1, CLOCK and PER2 (R).
Genetics and GSK3B
Top GSK3 beta Inhibitors
- Curcumin (R)
- Quercetin (R)
- Luteolin (potent) (R)
- Apigenin (potent) (R)
- Cinnamon (R)
- Angelica Sinensis (R)
- Intranasal insulin (normalized high GSK3b in diabetic animals) (R)
What Increases GSK3b
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