title: Anti-LRP/LR specific antibody IgG1-iS18 and knock-down of LRP/LR by shRNAs rescue cells from Aβ42 induced cytotoxicity.
abstract: Alzheimer's disease (AD) is characterized by neurofibrillary tangles, senile plaques and neuronal loss. Amyloid beta (Aβ) is proposed to elicit neuronal loss through cell surface receptors. As Aβ shares common binding partners with the 37 kDa/67 kDa laminin receptor (LRP/LR), we investigated whether these proteins interact and the pathological significance of this association. An LRP/LR-Αβ42 interaction was assessed by immunofluorescence microscopy and pull down assays. The cell biological effects were investigated by 3-(4,5-Dimethylthaizol-2-yl)-2,5-diphenyltetrazolium bromide and Bromodeoxyuridine assays. LRP/LR and Αβ42 co-localised on the cell surface and formed immobilized complexes suggesting an interaction. Antibody blockade by IgG1-iS18 and shRNA mediated down regulation of LRP/LR significantly enhanced cell viability and proliferation in cells co-treated with Αβ42 when compared to cells incubated with Αβ42 only. Results suggest that LRP/LR is implicated in Αβ42 mediated cytotoxicity and that anti-LRP/LR specific antibodies and shRNAs may serve as potential therapeutic tools for AD.
authors.affiliation: School of Molecular and Cell Biology, University of the Witwatersrand, Private Bag 3, Wits 2050, Johannesburg, Republic of South Africa.
authors.forename: Bianca
authors.initials: B
authors.lastname: Da Costa Dias
authors.forename: Katarina
authors.initials: K
authors.lastname: Jovanovic
authors.forename: Danielle
authors.initials: D
authors.lastname: Gonsalves
authors.forename: Kiashanee
authors.initials: K
authors.lastname: Moodley
authors.forename: Uwe
authors.initials: U
authors.lastname: Reusch
authors.forename: Stefan
authors.initials: S
authors.lastname: Knackmuss
authors.forename: Clement
authors.initials: C
authors.lastname: Penny
authors.forename: Marc S
authors.initials: MS
authors.lastname: Weinberg
authors.forename: Melvyn
authors.initials: M
authors.lastname: Little
authors.forename: Stefan F T
authors.initials: SF
authors.lastname: Weiss
mesh_terms: D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D002460:Cell Line; D002462:Cell Membrane; D015536:Down-Regulation; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D006801:Humans; D011485:Protein Binding; D021381:Protein Transport; D034741:RNA, Small Interfering / Q000235:genetics* / Q000378:metabolism; D017474:Receptors, Laminin / Q000037:antagonists & inhibitors* / Q000235:genetics* / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D000911:Antibodies, Monoclonal; D034741:RNA, Small Interfering; D017474:Receptors, Laminin
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