title: The neuronal calcium sensor protein VILIP-1 is associated with amyloid plaques and extracellular tangles in Alzheimer's disease and promotes cell death and tau phosphorylation in vitro: a link between calcium sensors and Alzheimer's disease?
abstract: To investigate whether the observed association of intracellular neuronal calcium sensor (NCS) proteins with amyloid plaques and neurofibrillar tangles in Alzheimer brains is linked to a possible neuroprotective or neurotoxic activity of the protein, we performed cytotoxicity tests in PC12 cells transfected with the calcium sensor protein VILIP-1 (visinin-like protein) and the calcium buffer protein calbindin-D28K. Whereas VILIP-1 expression enhanced the neurotoxic effect of ionomycin already at low ionophore concentrations, calbindin-D28K protected against ionomycin-induced cytotoxicity only at high ionomycin and therefore calcium concentrations. However, in double-transfected cells calbindin-D28K rescued VILIP-1-mediated cytotoxicity at low ionomycin concentrations. Since VILIP-1 was found to be associated with fibrillar tangles in Alzheimer brains, we tested whether VILIP-1 has an influence on tau hyperphosphorylation. VILIP-1 expression enhanced hyperphosphorylation of tau protein compared to nontransfected or calbindin-D28K-transfected cells. These results raise the possibility that the observed reduction in VILIP-1-expressing cells may indicate a selective vulnerability of these neurons and that the calcium sensor protein is involved in the pathophysiology of Alzheimer's disease. The calcium sensor protein may influence tau phosphorylation and have a role in calcium-mediated neurotoxicity opposed to the previously discovered protective effect of calcium buffer proteins.
authors.affiliation: Research Institute for Applied Neuroscience, FAN GmbH, Magdeburg, Germany.
authors.forename: I
authors.initials: I
authors.lastname: Schnurra
authors.forename: H G
authors.initials: HG
authors.lastname: Bernstein
authors.forename: P
authors.initials: P
authors.lastname: Riederer
authors.forename: K H
authors.initials: KH
authors.lastname: Braunewell
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001921:Brain / Q000473:pathology; D001923:Brain Chemistry; D064092:Calbindin 1; D064026:Calbindins; D002118:Calcium / Q000502:physiology*; D020013:Calcium Signaling / Q000502:physiology*; D002135:Calcium-Binding Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D006801:Humans; D015759:Ionomycin / Q000633:toxicity; D007476:Ionophores / Q000633:toxicity; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D051596:Neurocalcin; D016874:Neurofibrillary Tangles / Q000737:chemistry*; D016716:PC12 Cells / Q000378:metabolism; D010766:Phosphorylation; D058225:Plaque, Amyloid / Q000737:chemistry*; D011499:Protein Processing, Post-Translational; D011817:Rabbits; D051381:Rats; D044169:Receptors, Calcium-Sensing; D011993:Recombinant Fusion Proteins / Q000502:physiology; D064030:S100 Calcium Binding Protein G / Q000235:genetics / Q000502:physiology; D014162:Transfection; D016875:tau Proteins / Q000378:metabolism*
chemical_list: C576498:CALB1 protein, human; C576500:Calb1 protein, rat; D064092:Calbindin 1; D064026:Calbindins; D002135:Calcium-Binding Proteins; D007476:Ionophores; D009419:Nerve Tissue Proteins; D051596:Neurocalcin; D044169:Receptors, Calcium-Sensing; D011993:Recombinant Fusion Proteins; D064030:S100 Calcium Binding Protein G; C496688:VSNL1 protein, human; C496690:Vsnl1 protein, rat; D016875:tau Proteins; D015759:Ionomycin; D002118:Calcium