GSK3β Regulates Brain Energy Metabolism

Martin, Stephen A.; Souder, Dylan C.; Miller, Karl; Clark, Josef P.; Sagar, Abdul Kader; Eliceiri, Kevin W.; Puglielli, Luigi; Beasley, T. Mark; Anderson, Rozalyn M.

doi:10.1016/j.celrep.2018.04.045

Cited by 58 publications

(44 citation statements)

References 45 publications

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“…Moreover, GSK3β inhibition alters PGC-1α protein stability, localization, and activity. These studies support the idea that GSK3β may be important in neuronal metabolic integrity [ 55 ].…”

Section: Role Of Gsk3β Signaling In Neuronssupporting

confidence: 85%

“…GSK3β regulates PGC-1α stability through phosphorylation, which can be recognized by the E3 ubiquitin ligase [ 54 ]. Several studies have shown that GSK3β regulates mitochondrial energy metabolism in the neurons and glia [ 55 ]. Moreover, GSK3β inhibition increases mitochondrial respiration and membrane potential, and alters NAD(P)H metabolism in the neurons.…”

Section: Role Of Gsk3β Signaling In Neuronsmentioning

confidence: 99%

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Recent Advances on the Role of GSK3β in the Pathogenesis of Amyotrophic Lateral Sclerosis

et al. 2020

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Amyotrophic lateral sclerosis (ALS) is a common neurodegenerative disease characterized by progressive motor neuron degeneration. Although several studies on genes involved in ALS have substantially expanded and improved our understanding of ALS pathogenesis, the exact molecular mechanisms underlying this disease remain poorly understood. Glycogen synthase kinase 3 (GSK3) is a multifunctional serine/threonine-protein kinase that plays a critical role in the regulation of various cellular signaling pathways. Dysregulation of GSK3β activity in neuronal cells has been implicated in the pathogenesis of neurodegenerative diseases. Previous research indicates that GSK3β inactivation plays a neuroprotective role in ALS pathogenesis. GSK3β activity shows an increase in various ALS models and patients. Furthermore, GSK3β inhibition can suppress the defective phenotypes caused by SOD, TDP-43, and FUS expression in various models. This review focuses on the most recent studies related to the therapeutic effect of GSK3β in ALS and provides an overview of how the dysfunction of GSK3β activity contributes to ALS pathogenesis.

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Section: Role Of Gsk3β Signaling In Neuronssupporting

confidence: 85%

Section: Role Of Gsk3β Signaling In Neuronsmentioning

confidence: 99%

Recent Advances on the Role of GSK3β in the Pathogenesis of Amyotrophic Lateral Sclerosis

et al. 2020

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“…GSK3β is a serine/threonine protein kinase with broad expression and one of the downstream targets of Akt. It is essential in energy metabolism (Martin et al, 2018) and nerve cell development (Chen et al, 2019a). The levels of GSK3β can be decreased by phosphorylation at the ser9 site (Xu et al, 2017;Chen et al, 2019b).…”

Section: Discussionmentioning

confidence: 99%

Treatment With Liraglutide Exerts Neuroprotection After Hypoxic–Ischemic Brain Injury in Neonatal Rats via the PI3K/AKT/GSK3β Pathway

Zeng

Bai

Jiang

et al. 2020

Front. Cell. Neurosci.

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Neonatal hypoxic-ischemic (HI) brain injury is a detrimental disease, which results in high mortality and long-term neurological deficits. Nevertheless, the treatment options for this disease are limited. Thus, the aim of the present study was to assess the role of liraglutide in neonatal HI brain injury in rats and investigate the associated mechanisms. The results showed that treatment with liraglutide significantly reduced infarct volume and ameliorated cerebral edema, decreased inflammatory response, promoted the recovery of tissue structure, and improved prognosis following HI brain injury. Moreover, treatment with liraglutide inhibited apoptosis and promoted neuronal survival both in the rat model and following oxygen-glucose deprivation (OGD) insult. LY294002, an inhibitor of phosphoinositide 3-kinase (PI3K), partially reversed these therapeutic effects, suggesting that the PI3K/protein kinase B (Akt) pathway was involved. In conclusion, our data revealed that treatment with liraglutide exerts neuroprotection after neonatal HI brain injury via the PI3K/Akt/glycogen synthase kinase-3β (GSK3β) pathway and may be a promising therapy for this disease.

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“…Since p-tau S396 did not significantly change with 12 weeks of aerobic training, other pathologic phosphoepitopes induced by GSK3β Y216 could be evaluated with further study. Another possibility of the mismatch between the levels of phosphorylated tau and p-GSK3βY216 could be the long-term effects of aerobic training on brain metabolism, since GSK3β plays a crucial role in metabolism [26]. In fact, the level of IRS-1 in the IC of RG was significantly higher than that of SG, indicating that a 12-week aerobic training may regulate brain metabolism as well as tau protein modification.…”

Section: Discussionmentioning

confidence: 99%

Effects of Aerobic Exercise on Tau and Related Proteins in Rats with the Middle Cerebral Artery Occlusion

Mankhong

Kim

Moon

et al. 2020

IJMS

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Although Alzheimer’s disease (AD)-like pathology is frequently found in patients with post-stroke dementia, little is known about the effects of aerobic exercise on the modifications of tau and related proteins. Therefore, we evaluated the effects of aerobic exercise on the phosphorylation and acetylation of tau and the expressions of tau-related proteins, after middle cerebral artery occlusion (MCAO) stroke. Twenty-four Sprague–Dawley rats with MCAO infarction were used in this study. The rehabilitation group (RG) received treadmill training 40 min/day for 12 weeks, whereas the sedentary group (SG) did not receive any type of training. Functional tests, such as the single pellet reaching task, rotarod, and radial arm maze tests, were performed monthly for 3 months. In ipsilateral cortices in the RG and SG groups, level of Ac-tau was lower in the RG, whereas levels of p-tauS396, p-tauS262, and p-tauS202/T205 were not significantly lower in the RG. Level of phosphorylated glycogen synthase kinase 3-beta Tyr 216 (p-GSK3βY216) was lower in the RG, but levels of p-AMPK and phosphorylated glycogen synthase kinase 3-beta Ser 9 (p-GSK3βS9) were not significantly lower. Levels of COX-2 and BDNF were not significantly different between the two groups, while SIRT1 significantly decreased in ipsilateral cortices in RG. In addition, aerobic training also improved motor, balance, and memory functions. Rehabilitation with aerobic exercise inhibited tau modification, especially tau acetylation, following infarction in the rat MCAO model, which was accompanied with the improvement of motor and cognitive functions.

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GSK3β Regulates Brain Energy Metabolism

Cited by 58 publications

References 45 publications

Recent Advances on the Role of GSK3β in the Pathogenesis of Amyotrophic Lateral Sclerosis

Recent Advances on the Role of GSK3β in the Pathogenesis of Amyotrophic Lateral Sclerosis

Treatment With Liraglutide Exerts Neuroprotection After Hypoxic–Ischemic Brain Injury in Neonatal Rats via the PI3K/AKT/GSK3β Pathway

Effects of Aerobic Exercise on Tau and Related Proteins in Rats with the Middle Cerebral Artery Occlusion

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