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Title: Novel protein kinase inhibitors related to tau pathology modulate tau protein-self interaction using a luciferase complementation assay
Author(s): Holzer, Max
Schade, Nico
Opitz, Ansgar
Hilbrich, Isabel
Stieler, Jens
Vogel, Tim
Neukel, Valentina
Oberstadt, Moritz
Totzke, Frank
Schächtele, Christoph
Sippl, WolfgangLook up in the Integrated Authority File of the German National Library
Hilgeroth, AndreasLook up in the Integrated Authority File of the German National Library
Issue Date: 2018
Type: Article
Language: English
Abstract: The current number of drugs available for the treatment of Alzheimer’s disease (AD) is strongly limited and their benefit for therapy is given only in the early state of the disease. An effective therapy should affect those processes which mainly contribute to the neuronal decay. There have been many approaches for a reduction of toxic Aβ peptides which mostly failed to halt cognitive deterioration in patients. The formation of neurofibrillary tangles (NFT) and its precursor tau oligomers have been suggested as main cause of neuronal degeneration because of a direct correlation of their density to the degree of dementia. Reducing of tau aggregation may be a viable approach for the treatment of AD. NFT consist of hyperphosphorylated tau protein and tau hyperphosphorylation reduces microtubule binding. Several protein kinases are discussed to be involved in tau hyperphosphorylation. We developed novel inhibitors of three protein kinases (gsk-3β, cdk5, and cdk1) and discussed their activity in relation to tau phosphorylation and on tau–tau interaction as a nucleation stage of a tau aggregation in cells. Strongest effects were observed for those inhibitors with effects on all the three kinases with emphasis on gsk-3β in nanomolar ranges.
Open Access: Open access publication
License: (CC BY 4.0) Creative Commons Attribution 4.0(CC BY 4.0) Creative Commons Attribution 4.0
Sponsor/Funder: Publikationsfond MLU
Journal Title: Molecules
Publisher: MDPI
Publisher Place: Basel
Volume: 32
Issue: 9
Original Publication: 10.3390/molecules23092335
Appears in Collections:Open Access Publikationen der MLU

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