title: Ion Channel Formation by Tau Protein: Implications for Alzheimer's Disease and Tauopathies.
abstract: Tau is a microtubule associated protein implicated in the pathogenesis of several neurodegenerative diseases. Because of the channel forming properties of other amyloid peptides, we employed planar lipid bilayers and atomic force microscopy to test tau for its ability to form ion permeable channels. Our results demonstrate that tau can form such channels, but only under acidic conditions. The channels formed are remarkably similar to amyloid peptide channels in their appearance, physical and electrical size, permanence, lack of ion selectivity, and multiple channel conductances. These channels differ from amyloid channels in their voltage dependence and resistance to blockade by zinc ion. These channels could explain tau's pathologic role in disease by lowering membrane potential, dysregulating calcium, depolarizing mitochondria, or depleting energy stores. Tau might also combine with amyloid beta peptides to form toxic channels.
authors.affiliation: Departments of Bioengineering and Mechanical & Aerospace Engineering, University of California at San Diego , La Jolla, California 92093, United States.
authors.forename: Nirav
authors.initials: N
authors.lastname: Patel
authors.affiliation: Departments of Bioengineering and Mechanical & Aerospace Engineering, University of California at San Diego , La Jolla, California 92093, United States.
authors.forename: Srinivasan
authors.initials: S
authors.lastname: Ramachandran
authors.affiliation: Department of Psychiatry, David Geffen School of Medicine, Semel Institute for Neuroscience & Human Behavior, University of California , Los Angeles, California 90095, United States.
authors.forename: Rustam
authors.initials: R
authors.lastname: Azimov
authors.affiliation: Department of Psychiatry, David Geffen School of Medicine, Semel Institute for Neuroscience & Human Behavior, University of California , Los Angeles, California 90095, United States.
authors.forename: Bruce L
authors.initials: BL
authors.lastname: Kagan
authors.affiliation: Departments of Bioengineering and Mechanical & Aerospace Engineering, University of California at San Diego , La Jolla, California 92093, United States.
authors.forename: Ratnesh
authors.initials: R
authors.lastname: Lal
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D007473:Ion Channels / Q000378:metabolism*; D008051:Lipid Bilayers; D018625:Microscopy, Atomic Force; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D007473:Ion Channels; D008051:Lipid Bilayers; D016875:tau Proteins