NAP protects memory, increases soluble tau and reduces tau hyperphosphorylation in a tauopathy model.
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 approximately 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.
Shiryaev
Natalia
N
The Adams Super Center for Brain Studies, Department of Human Molecular Genetics and Biochemistry, Tel Aviv University, Israel.
Jouroukhin
Yan
Y
Giladi
Eliezer
E
Polyzoidou
Eleni
E
Grigoriadis
Nikolaos C
NC
Rosenmann
Hanna
H
Gozes
Illana
I
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D019610:Cytoprotection / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D006801:Humans; D066298:In Vitro Techniques; D008569:Memory Disorders / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D016874:Neurofibrillary Tangles / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D009842:Oligopeptides / Q000494:pharmacology* / Q000627:therapeutic use; D010766:Phosphorylation / Q000187:drug effects; D012995:Solubility / Q000187:drug effects; D024801:Tauopathies / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D016896:Treatment Outcome; D016875:tau Proteins / Q000187:drug effects* / Q000378:metabolism
D018696:Neuroprotective Agents; D009842:Oligopeptides; D016875:tau Proteins; C425904:davunetide