Human Polymerase δ-Interacting Protein 2 (PolDIP2) Inhibits the Formation of Human Tau Oligomers and Fibrils

Int J Mol Sci. 2021 May 28;22(11):5768. doi: 10.3390/ijms22115768.

Abstract

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.

Keywords: PolDIP2; Tau; amyloid.

MeSH terms

  • Alzheimer Disease / genetics
  • Alzheimer Disease / metabolism*
  • Amyloid / metabolism*
  • Amyloid beta-Peptides / metabolism
  • Benzothiazoles
  • Brain / metabolism
  • Humans
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Tauopathies
  • tau Proteins / metabolism*

Substances

  • Amyloid
  • Amyloid beta-Peptides
  • Benzothiazoles
  • Nuclear Proteins
  • POLDIP2 protein, human
  • tau Proteins
  • thioflavin T