TY - JOUR
T1 - NAP protects memory, increases soluble tau and reduces tau hyperphosphorylation in a tauopathy model
AU - Shiryaev, Natalia
AU - Jouroukhin, Yan
AU - Giladi, Eliezer
AU - Polyzoidou, Eleni
AU - Grigoriadis, Nikolaos C.
AU - Rosenmann, Hanna
AU - Gozes, Illana
PY - 2009/5
Y1 - 2009/5
N2 - 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.
AB - 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.
KW - Alzheimer's disease
KW - Drug candidate
KW - NAP
KW - Neurodegenerative disease
KW - Tau
KW - Tauopathy
UR - http://www.scopus.com/inward/record.url?scp=64649097649&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=64649097649&partnerID=8YFLogxK
U2 - 10.1016/j.nbd.2009.02.011
DO - 10.1016/j.nbd.2009.02.011
M3 - Article
C2 - 19264130
AN - SCOPUS:64649097649
SN - 0969-9961
VL - 34
SP - 381
EP - 388
JO - Neurobiology of Disease
JF - Neurobiology of Disease
IS - 2
ER -