PuSH - Publikationsserver des Helmholtz Zentrums München

Chandupatla, R.R.* ; Flatley, A. ; Feederle, R. ; Mandelkow, E.M.* ; Kaniyappan, S.*

Novel antibody against low-n oligomers of tau protein promotes clearance of tau in cells via lysosomes.

Alzheimers Dement. 6:e12097 (2020)
Verlagsversion DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
Introduction: Tau, a natively unfolded soluble protein, forms abnormal oligomers and insoluble filaments in several neurodegenerative diseases, including Alzheimer disease (AD). Tau-induced toxicity is mainly due to oligomers rather than monomers or fibrils. Methods: We have developed monoclonal antibodies against purified low-n tau oligomers of the tau repeat domain as a tool to neutralize tau aggregation and toxicity. In vitro aggregation inhibition was tested by thioflavin S, dynamic light scattering (DLS), and atomic force microscopy (AFM). Using a split-luciferase complementation assay and fluorescence-activated cell sorting (FACS), the inhibition of aggregation was analyzed in an N2a cell model of tauopathy. Results: Antibodies inhibited tau aggregation in vitro up to ~90% by blocking tau at an oligomeric state. Some antibodies were able to block tau dimerization/oligomerization in cells, as measured by a split-luciferase complementation assay. Antibodies applied extracellularly were internalized and led to sequestration of tau into lysosomes for degradation. Discussion: Novel low-n tau oligomer specific monoclonal antibody inhibits Tau oligomerization in cells and promotes toxic tau clearance.
Altmetric
Weitere Metriken?
Zusatzinfos bearbeiten [➜Einloggen]
Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Aggregation ; Antibody ; N2a Cells ; Screening ; Tau
ISSN (print) / ISBN 1552-5260
e-ISSN 1552-5279
Quellenangaben Band: 6, Heft: 1, Seiten: , Artikelnummer: e12097 Supplement: ,
Verlag Elsevier
Verlagsort New York, NY [u.a.]
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) CF Monoclonal Antibodies (CF-MAB)