title: GSPE interferes with tau aggregation in vivo: implication for treating tauopathy.
abstract: Tauopathies are characterized by progressive neurodegeneration caused by intracellular accumulation of hyperphosphorylated tau protein aggregates in the brain. The present study was designed to test whether a grape seed polyphenolic extract (GSPE) previously shown to inhibit tau protein aggregation in vitro could benefit tau-mediated neuropathology and behavior deficits in JNPL3 transgenic mice expressing a human tau protein containing the P301L mutation. Nine-month-old JNPL3 mice were treated with GSPE delivered through their drinking water for 6 months. We found that GSPE treatment significantly reduced the number of motor neurons immunoreactive for hyperphosphorylated and conformationally-modified tau in the ventral horns of the spinal cord identified using AT100, PHF-1, AT8, and Alz50 tau antibodies. This coincided with a drastically reduced level of hyperphosphorylated and sarcosyl-insoluble tau in spinal cord fractions. Furthermore, the reduction of tau pathology was accompanied by an improvement in the motor function assessed by a wire hang test. Collectively, our results suggest that GSPE can interfere with tau-mediated neurodegenerative mechanisms and ameliorate neurodegenerative phenotype in an animal model of tauopathy. Our studies support further evaluation of GSPE for preventing and/or treating of tauopathies in humans.
authors: Department of Neurology, Mount Sinai School of Medicine, New York, NY 10029, USA.
authors: Ismael
authors: I
authors: Santa-Maria
authors: Carmen
authors: C
authors: Diaz-Ruiz
authors: Hanna
authors: H
authors: Ksiezak-Reding
authors: Alice
authors: A
authors: Chen
authors: Lap
authors: L
authors: Ho
authors: Jun
authors: J
authors: Wang
authors: Giulio Maria
authors: GM
authors: Pasinetti
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D056604:Grape Seed Extract / Q000627:therapeutic use*; D006801:Humans; D007930:Leucine / Q000235:genetics; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008970:Molecular Weight; D009154:Mutation / Q000235:genetics; D059808:Polyphenols / Q000627:therapeutic use; D011392:Proline / Q000235:genetics; D011597:Psychomotor Performance / Q000187:drug effects; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism; D024801:Tauopathies / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D056604:Grape Seed Extract; C054369:MAPT protein, human; D059808:Polyphenols; D016875:tau Proteins; D011392:Proline; D007930:Leucine