Protein kinase G phosphorylates the Alzheimer's disease-associated tau protein at distinct Ser/Thr sites

G. Montalto, F. Caudano, L. Sturla, S. Bruzzone, A. Salis, G. Damonte, J. Prickaerts, E. Fedele, R. Ricciarelli*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Intraneuronal accumulation of hyperphosphorylated tau is a pathological hallmark of several neurodegenerative disorders, including Alzheimer's disease. Phosphorylation plays a crucial role in modulating the tau-microtubule interaction and the ability of the protein to aggregate, but despite efforts during the past decades, the real identity of the kynases involved in vivo remains uncertain. Here, for the first time, we demonstrate that the cGMP-dependent protein kinase G (PKG) phosphorylates tau in both in vitro and in vivo models. More intriguingly, we provide evidence that PKG phosphorylates tau at Ser214 but not at Ser202, a condition that could reduce the pathological aggregation of the protein shifting tau from a pro-aggregant to a neuroprotective anti-aggregant conformation.
Original languageEnglish
Pages (from-to)126-134
Number of pages9
JournalBiofactors
Volume47
Issue number1
DOIs
Publication statusPublished - 1 Jan 2021

Keywords

  • Alzheimer's disease
  • alzheimer's disease
  • cGMP
  • cgmp
  • phosphodiesterase 5 inhibitors
  • tau
  • vardenafil
  • CYCLIC ADENOSINE-MONOPHOSPHATE
  • TIME
  • MEMORY
  • ABILITY
  • CGMP
  • AGGREGATION
  • CAMP

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