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Region Hovedstaden - en del af Københavns Universitetshospital
Udgivet

Prostate stem cell antigen interacts with nicotinic acetylcholine receptors and is affected in Alzheimer's disease

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  1. Striking reduction in neurons and glial cells in anterior thalamic nuclei of older patients with Down syndrome

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  2. The total number of myelinated nerve fibers is reduced in corpus callosum in brains from patients with Alzheimer's disease

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  3. The effect of long-term treatment with coenzyme Q10 on nucleic acid modifications by oxidation in children with Down syndrome

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  1. MR-vejledt laserablation til behandling af hjernetumorer og epilepsi

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  2. A high-resolution in vivo atlas of the human brain's benzodiazepine binding site of GABAA receptors

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  3. 7T Epilepsy Task Force Consensus Recommendations on the Use of 7T MRI in Clinical Practice

    Publikation: Bidrag til tidsskriftReviewForskningpeer review

  4. Extensive astrocyte metabolism of γ-aminobutyric acid (GABA) sustains glutamine synthesis in the mammalian cerebral cortex

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Vis graf over relationer

Alzheimer's disease (AD) is a neurodegenerative disorder involving impaired cholinergic neurotransmission and dysregulation of nicotinic acetylcholine receptors (nAChRs). Ly-6/neurotoxin (Lynx) proteins have been shown to modulate cognition and neural plasticity by binding to nAChR subtypes and modulating their function. Hence, changes in nAChR regulatory proteins such as Lynx proteins could underlie the dysregulation of nAChRs in AD. Using Western blotting, we detected bands corresponding to the Lynx proteins prostate stem cell antigen (PSCA) and Lypd6 in human cortex indicating that both proteins are present in the human brain. We further showed that PSCA forms stable complexes with the α4 nAChR subunit and decreases nicotine-induced extracellular-signal regulated kinase phosphorylation in PC12 cells. In addition, we analyzed protein levels of PSCA and Lypd6 in postmortem tissue of medial frontal gyrus from AD patients and found significantly increased PSCA levels (approximately 70%). In contrast, no changes in Lypd6 levels were detected. In concordance with our findings in AD patients, PSCA levels were increased in the frontal cortex of triple transgenic mice with an AD-like pathology harboring human transgenes that cause both age-dependent β-amyloidosis and tauopathy, whereas Tg2576 mice, which display β-amyloidosis only, had unchanged PSCA levels compared to wild-type animals. These findings identify PSCA as a nAChR-binding protein in the human brain that is affected in AD, suggesting that PSCA-nAChR interactions may be involved in the cognitive dysfunction observed in AD.

OriginalsprogEngelsk
TidsskriftNeurobiology of Aging
Vol/bind36
Udgave nummer4
Sider (fra-til)1629-38
Antal sider10
ISSN0197-4580
DOI
StatusUdgivet - apr. 2015

ID: 45588956