title: Intracellular and extracellular microtubule associated protein tau as a therapeutic target in Alzheimer disease and other tauopathies.
abstract: BACKGROUND
  Microtubule associated protein tau, a protein mainly expressed in neurons, plays an important role in several diseases related to dementia, named tauopathies. Alzheimer disease is the most relevant tauopathy. The role of tau protein in dementia is now a topic under discussion, and is the focus of this review.
  
  
  METHODS
  We have covered two major areas: tau pathology and tau as a therapeutic target. Tau pathology is mainly related to a gain of toxic function due to an abnormal accumulation, aberrant modifications (such as hyperphosphorylation and truncation, among others) and self-aggregation of tau into oligomers or larger structures. Also, tau can be found extracellularly in a toxic form. Tau-based therapy is mainly centered on avoiding the gain of these toxic functions of tau.
  
  
  CONCLUSIONS
  Tau therapies are focused on lowering tau levels, mainly of modified tau species that could be toxic for neurons (phosphorylated, truncated or aggregated tau), in intracellular or extracellular form. Decreasing the levels of those toxic species is a possible therapeutic strategy.
authors.affiliation: a Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED) , Madrid , Spain.|b Centro de Biología Molecular 'Severo Ochoa' CSIC-UAM , Madrid , Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Avila
authors.affiliation: a Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED) , Madrid , Spain.|b Centro de Biología Molecular 'Severo Ochoa' CSIC-UAM , Madrid , Spain.
authors.forename: Noemí
authors.initials: N
authors.lastname: Pallas
authors.affiliation: a Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED) , Madrid , Spain.|b Centro de Biología Molecular 'Severo Ochoa' CSIC-UAM , Madrid , Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Bolós
authors.affiliation: c Centre for Biomedical Research of the Canary Islands (CIBICAN), Institute for Biomedical Technologies (ITB) , University of La Laguna (ULL) , Tenerife , Spain.
authors.forename: C Laura
authors.initials: CL
authors.lastname: Sayas
authors.affiliation: a Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED) , Madrid , Spain.|b Centro de Biología Molecular 'Severo Ochoa' CSIC-UAM , Madrid , Spain.
authors.forename: Felix
authors.initials: F
authors.lastname: Hernandez
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000503:physiopathology; D000818:Animals; D006801:Humans; D058990:Molecular Targeted Therapy; D009474:Neurons / Q000378:metabolism; D010766:Phosphorylation; D024801:Tauopathies / Q000188:drug therapy / Q000503:physiopathology; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016875:tau Proteins
keywords: Alzheimer disease; MAPT; tau protein; tauopathies; toxic gain of function