TY - JOUR
T1 - Human polymerase δ-interacting protein 2 (Poldip2) inhibits the formation of human tau oligomers and fibrils
AU - Kasho, Kazutoshi
AU - Krasauskas, Lukas
AU - Smirnovas, Vytautas
AU - Stojkovič, Gorazd
AU - Morozova-Roche, Ludmilla A.
AU - Wanrooij, Sjoerd
N1 - Funding Information:
Funding: This research was funded by the Swedish Medical Research Council, Forskningsstrategiska medel, Medical Faculty, Umeå University, Insamlingsstiftelsen (L.A.M-R.), JSPS Overseas Research Fellowship 201860287 (K.K.), Knut and Alice Wallenberg Foundation (KAW 2019.0307, to S.W.), Swedish Research Council (2018-02781, to S.W.) and G.S. was supported by the Kempe Foundation (JCK-1831).
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2021/6/1
Y1 - 2021/6/1
N2 - A central characteristic of Alzheimer’s disease (AD) and other tauopathies is the accumulation of aggregated and misfolded Tau deposits in the brain. Tau-targeting therapies for AD have been unsuccessful in patients to date. Here we show that human polymerase δ-interacting protein 2 (PolDIP2) interacts with Tau. With a set of complementary methods, including thioflavin-T-based aggregation kinetic assays, Tau oligomer-specific dot-blot analysis, and single oligomer/fibril analysis by atomic force microscopy, we demonstrate that PolDIP2 inhibits Tau aggregation and amyloid fibril growth in vitro. The identification of PolDIP2 as a potential regulator of cellular Tau aggregation should be considered for future Tau-targeting therapeutics.
AB - A central characteristic of Alzheimer’s disease (AD) and other tauopathies is the accumulation of aggregated and misfolded Tau deposits in the brain. Tau-targeting therapies for AD have been unsuccessful in patients to date. Here we show that human polymerase δ-interacting protein 2 (PolDIP2) interacts with Tau. With a set of complementary methods, including thioflavin-T-based aggregation kinetic assays, Tau oligomer-specific dot-blot analysis, and single oligomer/fibril analysis by atomic force microscopy, we demonstrate that PolDIP2 inhibits Tau aggregation and amyloid fibril growth in vitro. The identification of PolDIP2 as a potential regulator of cellular Tau aggregation should be considered for future Tau-targeting therapeutics.
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U2 - 10.3390/ijms22115768
DO - 10.3390/ijms22115768
M3 - Article
C2 - 34071254
AN - SCOPUS:85106658099
VL - 22
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
SN - 1661-6596
IS - 11
M1 - 5768
ER -
