Affiliations: [a] Department of Psychiatry, Mount Sinai School of Medicine, New York, NY, USA | [b] Department of Neurology, Mount Sinai School of Medicine, New York, NY, USA | [c] Geriatric Research Education and Clinical Center, James J. Peters VA Medical Center, Bronx, NY, USA
Correspondence:
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Corresponding author: Giulio Maria Pasinetti, M.D., Ph.D., Annenberg Building, Room 14-94C, 1468 Madison Ave (at 100 Street), Mount Sinai School of Medicine, New York, NY 10029, USA. Tel.: +1 212 241 7398 or 212 241 5563; Fax: +1 212 876 9042; E-mail: [email protected].
Abstract: Abnormal misfoldings of the microtubule-associated protein tau, leading to the aggregation of tau into paired helical filaments that are ultimately deposited as neurofibrillary tangles, is a key neuropathologic feature of a number of neurodegenerative disorders collectively referred to as tauopathies. We recently observed that a particular grape seed polyphenolic extract (GSPE), namely, Meganatural-Az® may attenuate the generation and stability of misfolded proteins. We hypothesized that Meganatural-Az® GSPE might also attenuate tau protein misfolding that leads to the generation of tau filamentary aggregates that are critical for the initiation and progression of neurodegeneration and/or cognitive dysfunctions in tauopathies. In this study, we used in vitro aggregations of synthetic Ac-306VQIVYK311 tau peptide as a model system to explore whether Meganatural-Az® GSPE might modulate aggregations of tau protein. We demonstrate that this GSPE is capable of inhibiting tau peptide aggregations, as well as dissociating preformed tau peptide aggregates. Results from this study suggest that this GSPE might provide beneficial disease-modifying bioactivities in tau-associated neurodegenerative disorders by modulating tau-mediated neuropathologic mechanisms. Our observation, in conjunction with the demonstrated bioavailability, as well as safety and tolerability, of this GSPE, supports the development of Meganatural-Az® GSPE for the prevention and/or treatment of tau-associated neurodegenerative disorders.
