Selective α7 nicotinic acetylcholine receptor activation regulates glycogen synthase kinase3β and decreases tau phosphorylation in vivo

Bitner, Robert S.; Nikkel, Arthur L.; Markosyan, Stella; Otte, Stephani; Puttfarcken, Pamela S.; Gopalakrishnan, Murali

doi:10.1016/j.brainres.2009.01.069

Cited by 65 publications

(51 citation statements)

References 39 publications

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“…It was previously shown that phosphorylated ERK1/2 has a key role in activating CREB, a transcription factor involved in long-term memory formation (Adams and Sweatt, 2002). Further studies examined A-582941 to demonstrate that this a7 nAChR agonist induced an increase in phosphorylation of serine 9 on glycogen synthase kinase 3b (S9-GSKb), which was not observed in a7 nAChR knockout mice (Bitner et al, 2009). GSKb has been shown to be a predominant kinase in AD, involved in tau hyperphosphorylation (Grimes and Jope, 2001).…”

Section: F Modulation Of A7 Nicotinic Acetylcholine Receptor Signalingmentioning

confidence: 95%

“…GSKb has been shown to be a predominant kinase in AD, involved in tau hyperphosphorylation (Grimes and Jope, 2001). Additionally, A-582941 continuously infused subcutaneously to a steady-state exposure in Tg2576 mice, an AD model of amyloid precursor protein overexpression, significantly increased phosphorylation of S9-GSKb in hippocampus and in a double transgenic AD mouse (TAPP, tau P301L X amyloid precursor protein) decreased phosphorylation of tau (Bitner et al, 2009). Increased phosphorylation of ERK1/2, CREB, and S9-GSKb and decreased phosphorylation of tau were replicated with another a7 nAChR agonist of another chemotype (ABT-107) (Bitner et al, 2010).…”

Section: F Modulation Of A7 Nicotinic Acetylcholine Receptor Signalingmentioning

confidence: 99%

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Therapeutic Potential ofα7 Nicotinic Acetylcholine Receptors

et al. 2015

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Section: F Modulation Of A7 Nicotinic Acetylcholine Receptor Signalingmentioning

confidence: 95%

Section: F Modulation Of A7 Nicotinic Acetylcholine Receptor Signalingmentioning

confidence: 99%

Therapeutic Potential ofα7 Nicotinic Acetylcholine Receptors

et al. 2015

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“…The details of the preclinical validation studies of A-582941 were recently reported [138]. Very recently, Biter et al [139] reported that A-582941 can lead to increased phosphorylation of the inhibitory regulating amino acid residue Ser-9 on the glycogen synthase kinase3β (GSK3β), a major kinase responsible for tau hyperphosphorylation in the neuropathology of tauopathies such as front-temporal dementia and AD. A-582941 increased Ser-9 phosphorylation of GSK3β in the mouse cingulate cortex and hippocampus, and this increase in phosphorylation was not observed in α7 nAChR-knockout mice.…”

Section: Wyeth/siena Biotechmentioning

confidence: 99%

α7 Nicotinic Receptor Agonists: Potential Therapeutic Drugs for Treatment of Cognitive Impairments in Schizophrenia and Alzheimer’s Disease

Toyohara¹,

Hashimoto²

2010

Open Med Chem J

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Accumulating evidence suggests that α7 nicotinic receptors (α7 nAChRs), a subtype of nAChRs, play a role in the pathophysiology of neuropsychiatric diseases, including schizophrenia and Alzheimer’s disease (AD). A number of psychopharmacological and genetic studies shown that α7 nAChRs play an important role in the deficits of P50 auditory evoked potential in patients with schizophrenia, and that (α nAChR agonists would be potential therapeutic drugs for cognitive impairments associated with P50 deficits in schizophrenia. Furthermore, some studies have demonstrated that α7 nAChRs might play a key role in the amyloid-β (Aβ)-mediated pathology of AD, and that α7 nAChR agonists would be potential therapeutic drugs for Aβ deposition in the brains of patients with AD. Interestingly, the altered expression of α7 nAChRs in the postmortem brain tissues from patients with schizophrenia and AD has been reported. Based on all these findings, selective α7 nAChR agonists can be considered potential therapeutic drugs for cognitive impairments in both schizophrenia and AD. In this article, we review the recent research into the role of α7 nAChRs in the pathophysiology of these diseases and into the potential use of novel α7 nAChR agonists as therapeutic drugs.

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“…Briefly, the hippocampal regions were separated from the brains of neonatal rats within 2-3 min after sacrifice and maintained in Hibernate A Medium chilled on ice. After removing the meninges, the hippocampus was washed three times with Hank' s buffered saline solution and then digested with 0.25% trypsin for 10 min in 37 C. Subsequently, the incubation medium was discarded and DMEM containing 10% FBS was added to terminate digestion.…”

Section: Cell Cultures and Treatmentsmentioning

confidence: 99%

“…The supernatant, enzyme assay solution and WST buffer were added in the order indicated by the instructions for the kit. Following incubation at 37 C for 20 min, the absorbance at 450 nm was determined using a microplate reader and SOD activity calculated.…”

Section: à44ctmentioning

confidence: 99%

Original Research: Influence of okadaic acid on hyperphosphorylation of tau and nicotinic acetylcholine receptors in primary neurons

Zhao

Xiao

Wang

et al. 2016

Exp Biol Med (Maywood)

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The aim of the study was to investigate the influence of hyperphosphorylation of tau induced by okadaic acid on the expression of nicotinic acetylcholine receptors and the neurotoxicity of b-amyloid peptide. Primary cultures of neurons isolated from the hippocampus of the brains of neonatal rats were exposed to okadaic acid or/and Ab . Tau phosphorylated at Ser404 and Ser202, and the protein expressions of a7, a4 and a3 nAChR subunits were quantified by Western blotting, and their corresponding mRNAs by real-time PCR. Superoxide dismutase activity was assayed biochemically and malondialdehyde by thiobarbituric acid-reactive substance. As compared to controls, phosphorylations of tau at Ser404 and Ser202 in the neurons were elevated by exposure to 20 nM okadaic acid for 48 h but not by 1 or 2 mM Ab 1-42 . Treatment with 20 nM okadaic acid or 1 mM Ab 1-42 for 48 h resulted in the reduced a7, a4 and a3 proteins, and a4 and a3 mRNAs, as well as the decreased activity of superoxide dismutase and the increased malondialdehyde. Okadaic acid and Ab 1-42 together caused more pronounced changes in the expressions of a7 and a4, superoxide dismutase activity and lipid peroxidation than either alone. When pre-treatment with vitamin E or lovastatin, the neurotoxicity induced by okadaic acid was significantly attenuated. These findings indicate that hyperphosphorylation of tau induced by okadaic acid inhibits the expression of nicotinic acetylcholine receptors at both the protein and mRNA levels, as well as enhances the neurotoxicity of b-amyloid peptide.

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Selective α7 nicotinic acetylcholine receptor activation regulates glycogen synthase kinase3β and decreases tau phosphorylation in vivo

Cited by 65 publications

References 39 publications

Therapeutic Potential ofα7 Nicotinic Acetylcholine Receptors

Therapeutic Potential ofα7 Nicotinic Acetylcholine Receptors

α7 Nicotinic Receptor Agonists: Potential Therapeutic Drugs for Treatment of Cognitive Impairments in Schizophrenia and Alzheimer’s Disease

Original Research: Influence of okadaic acid on hyperphosphorylation of tau and nicotinic acetylcholine receptors in primary neurons

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