title: Therapeutic strategies for the treatment of tauopathies: Hopes and challenges.
abstract: A group of neurodegenerative diseases referred to as tauopathies are characterized by the presence of brain cells harboring inclusions of pathological species of the tau protein. These disorders include Alzheimer's disease and frontotemporal lobar degeneration due to tau pathology, including progressive supranuclear palsy, corticobasal degeneration, and Pick's disease. Tau is normally a microtubule (MT)-associated protein that appears to play an important role in ensuring proper axonal transport, but in tauopathies tau becomes hyperphosphorylated and disengages from MTs, with consequent misfolding and deposition into inclusions that mainly affect neurons but also glia. A body of experimental evidence suggests that the development of tau inclusions leads to the neurodegeneration observed in tauopathies, and there is a growing interest in developing tau-directed therapeutic agents. The following review provides a summary of strategies under investigation for the potential treatment of tauopathies, highlighting both the promises and challenges associated with these various therapeutic approaches.
authors.affiliation: Department of Pathology and Laboratory Medicine, Center for Neurodegenerative Disease Research, Institute on Aging, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Mansi R
authors.initials: MR
authors.lastname: Khanna
authors.affiliation: Department of Pathology and Laboratory Medicine, Center for Neurodegenerative Disease Research, Institute on Aging, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Jane
authors.initials: J
authors.lastname: Kovalevich
authors.affiliation: Department of Pathology and Laboratory Medicine, Center for Neurodegenerative Disease Research, Institute on Aging, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Virginia M-Y
authors.initials: VM
authors.lastname: Lee
authors.affiliation: Department of Pathology and Laboratory Medicine, Center for Neurodegenerative Disease Research, Institute on Aging, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: John Q
authors.initials: JQ
authors.lastname: Trojanowski
authors.affiliation: Department of Pathology and Laboratory Medicine, Center for Neurodegenerative Disease Research, Institute on Aging, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: kbrunden@upenn.edu.
authors.forename: Kurt R
authors.initials: KR
authors.lastname: Brunden
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000473:pathology; D001921:Brain / Q000473:pathology; D057174:Frontotemporal Lobar Degeneration / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D024801:Tauopathies / Q000188:drug therapy*; D016875:tau Proteins / Q000378:metabolism
chemical_list: D016875:tau Proteins
keywords: Alzheimer's disease; Amyloid; Drugs; Fibrils; Microtubules; Neurons; Tau; Tauopathy; Therapeutics