title: Alzheimer's amyloid-β peptide disturbs P2X7 receptor-mediated circadian oscillations of intracellular calcium.
abstract: Recent data indicate that Alzheimer's disease (AD) is associated with disturbances of the circadian rhythm in patients. We examined the effect of amyloid-β (Aβ) peptide, the main component of the senile plaques playing a critical role in the deregulation of calcium (Ca2+) homeostasis in AD, on the circadian oscillation of cytosolic calcium (Ca2+) levelsin vitro. The experiments we carried out in human primary skin fibroblasts. This cell line was previously shown to exhibit circadian rhythms of clock genes. Moreover, the basic clock properties of these peripheral cells closely mimic those measured physiologically and behaviorally in human and do not change during aging. In this study we showed that i) cytosolic Ca2+oscillations depend on the activation of purinergic P2X7 receptors; and ii) these oscillations are abolished in the presence of Aβ. In total, our new findings may help to deepen our understanding of the molecular mechanisms involved in AD-related circadian alterations.
authors.affiliation: Neurobiology Laboratory for Brain Aging and Mental Health, Transfaculty Research Platform, Molecular and Cognitive Neuroscience, University of Basel, Basel, Switzerland,. awilkaniec@imdik.pan.pl.|Psychiatric University Clinics, University of Basel, Basel, Switzerland.|Mossakowski Medical Research Center, Polish Academy of Sciences, Department of Cellular Signaling, Warsaw, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Wilkaniec
authors.affiliation: Neurobiology Laboratory for Brain Aging and Mental Health, Transfaculty Research Platform, Molecular and Cognitive Neuroscience, University of Basel, Basel, Switzerland.|Psychiatric University Clinics, University of Basel, Basel, Switzerland.
authors.forename: Karen
authors.initials: K
authors.lastname: Schmitt
authors.affiliation: Neurobiology Laboratory for Brain Aging and Mental Health, Transfaculty Research Platform, Molecular and Cognitive Neuroscience, University of Basel, Basel, Switzerland.|Psychiatric University Clinics, University of Basel, Basel, Switzerland.
authors.forename: Amandine
authors.initials: A
authors.lastname: Grimm
authors.affiliation: Mossakowski Medical Research Center, Polish Academy of Sciences, Department of Cellular Signaling, Warsaw, Poland.
authors.forename: Joanna B
authors.initials: JB
authors.lastname: Strosznajder
authors.affiliation: Neurobiology Laboratory for Brain Aging and Mental Health, Transfaculty Research Platform, Molecular and Cognitive Neuroscience, University of Basel, Basel, Switzerland.|Psychiatric University Clinics, University of Basel, Basel, Switzerland.
authors.forename: Anne
authors.initials: A
authors.lastname: Eckert
mesh_terms: D000375:Aging; D000544:Alzheimer Disease / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002940:Circadian Rhythm / Q000502:physiology*; D006801:Humans; D042541:Intracellular Space / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D058486:Receptors, Purinergic P2X7 / Q000378:metabolism*
chemical_list: C545487:APP protein, human; D016564:Amyloid beta-Protein Precursor; C546468:P2RX7 protein, human; D058486:Receptors, Purinergic P2X7; D002118:Calcium
keywords:  Alzheimer's disease;  P2X7 receptors;  calcium;  circadian rhythms; amyloid-β