Forskning
Udskriv Udskriv
Switch language
Region Hovedstaden - en del af Københavns Universitetshospital
Udgivet

Lynx1 and Aβ1-42 bind competitively to multiple nicotinic acetylcholine receptor subtypes

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  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

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Vis graf over relationer

Lynx1 regulates synaptic plasticity in the brain by regulating nicotinic acetylcholine receptors (nAChRs). It is not known to which extent Lynx1 can bind to endogenous nAChR subunits in the brain or how this interaction is affected by Alzheimer's disease pathology. We apply affinity purification to demonstrate that a water-soluble variant of human Lynx1 (Ws-Lynx1) isolates α3, α4, α5, α6, α7, β2, and β4 nAChR subunits from human and rat cortical extracts, and rat midbrain and olfactory bulb extracts, suggesting that Lynx1 forms complexes with multiple nAChR subtypes in the human and rodent brain. Incubation with Ws-Lynx1 decreases nicotine-mediated extracellular signal-regulated kinase phosphorylation in PC12 cells and striatal neurons, indicating that binding of Ws-Lynx1 is sufficient to inhibit signaling downstream of nAChRs. The effect of nicotine in PC12 cells is independent of α7 or α4β2 nAChRs, suggesting that Lynx1 can affect the function of native non-α7, non-α4β2 nAChR subtypes. We further show that Lynx1 and oligomeric β-amyloid1-42 compete for binding to several nAChR subunits, that Ws-Lynx1 prevents β-amyloid1-42-induced cytotoxicity in cortical neurons, and that cortical Lynx1 levels are decreased in a transgenic mouse model with concomitant β-amyloid and tau pathology. Our data suggest that Lynx1 binds to multiple nAChR subtypes in the brain and that this interaction might have functional and pathophysiological implications in relation to Alzheimer's disease.

OriginalsprogEngelsk
TidsskriftNeurobiology of Aging
Vol/bind46
Sider (fra-til)13-21
Antal sider9
ISSN0197-4580
DOI
StatusUdgivet - okt. 2016

ID: 49026882