NAP protects memory, increases soluble tau and reduces tau hyperphosphorylation in a tauopathy model

Natalia Shiryaev, Yan Jouroukhin, Eliezer Giladi, Eleni Polyzoidou, Nikolaos C. Grigoriadis, Hanna Rosenmann, Illana Gozes

Research output: Contribution to journalArticle

Abstract

NAP (NAPVSIPQ) provides broad neuroprotection through microtubule interaction. Here, NAP was investigated for neuroprotection in an in vivo tauopathy model. Transgenic mice (2-month-old) that express the human double mutant tau protein [P301S;K257T] fused to the tau promoter, were subjected to daily intranasal drug treatment for ∼ 5 months. Results showed increased performance in the NAP-treated mice compared to controls, as demonstrated in the Morris water maze, (p < 0.05). Treatment continued for 5 additional months and mouse cortices were biochemically analyzed. Protein extraction identified increased tau protein content in the heat-stable soluble fraction, which contains microtubule-associated tau, in the 1-year-old NAP-treated mice as compared to vehicle-controls. Tau phosphorylation (Ser 202) increased in the tau-transgenic mice compared to control mice, and was significantly reduced in NAP-treated mice. The current studies show for the first time activity for NAP in a "pure" tauopathy model, positioning it as a promising drug candidate in multiple neurodegenerative tauopathies.

Original languageEnglish (US)
Pages (from-to)381-388
Number of pages8
JournalNeurobiology of Disease
Volume34
Issue number2
DOIs
StatePublished - May 1 2009
Externally publishedYes

Fingerprint

Tauopathies
tau Proteins
Microtubules
Transgenic Mice
Mutant Proteins
Pharmaceutical Preparations
Hot Temperature
Phosphorylation
Water
Proteins

Keywords

  • Alzheimer's disease
  • Drug candidate
  • NAP
  • Neurodegenerative disease
  • Tau
  • Tauopathy

ASJC Scopus subject areas

  • Neurology

Cite this

NAP protects memory, increases soluble tau and reduces tau hyperphosphorylation in a tauopathy model. / Shiryaev, Natalia; Jouroukhin, Yan; Giladi, Eliezer; Polyzoidou, Eleni; Grigoriadis, Nikolaos C.; Rosenmann, Hanna; Gozes, Illana.

In: Neurobiology of Disease, Vol. 34, No. 2, 01.05.2009, p. 381-388.

Research output: Contribution to journalArticle

Shiryaev, N, Jouroukhin, Y, Giladi, E, Polyzoidou, E, Grigoriadis, NC, Rosenmann, H & Gozes, I 2009, 'NAP protects memory, increases soluble tau and reduces tau hyperphosphorylation in a tauopathy model', Neurobiology of Disease, vol. 34, no. 2, pp. 381-388. https://doi.org/10.1016/j.nbd.2009.02.011
Shiryaev, Natalia ; Jouroukhin, Yan ; Giladi, Eliezer ; Polyzoidou, Eleni ; Grigoriadis, Nikolaos C. ; Rosenmann, Hanna ; Gozes, Illana. / NAP protects memory, increases soluble tau and reduces tau hyperphosphorylation in a tauopathy model. In: Neurobiology of Disease. 2009 ; Vol. 34, No. 2. pp. 381-388.
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