title: Tau cleavage and tau aggregation in neurodegenerative disease.
abstract: Deposition of highly phosphorylated tau in the brain is the most significant neuropathological and biochemical characteristic of the group of neurodegenerative disorders termed the tauopathies. The discovery of tau fragments in these diseases suggests that tau cleavage and tau phosphorylation, both of which induce conformational changes in tau, could each have roles in disease pathogenesis. The identities of the proteases responsible for degrading tau, resulting in the appearance of truncated tau species in physiological and pathological conditions, are not known. Several fragments of tau are reported to have pro-aggregation properties, but the lack of disease-relevant cell models of tau aggregation has hampered investigation of the effects of tau aggregation on normal cellular functioning. In the present paper, we describe our findings of N-terminally truncated tau in the brain in a subgroup of the tauopathies in which tau isoforms containing four microtubule-binding domains predominate. We also discuss the evidence for the involvement of proteases in the generation of tau pathology in neurodegenerative disease, since these enzymes warrant further investigation as potential therapeutic targets in the tauopathies.
authors.affiliation: Department of Neuroscience, King's College London, Institute of Psychiatry, MRC Centre for Neurodegeneration Research, De Crespigny Park, London SE5 8AF, UK. diane.hanger@kcl.ac.uk
authors.forename: Diane P
authors.initials: DP
authors.lastname: Hanger
authors.forename: Selina
authors.initials: S
authors.lastname: Wray
mesh_terms: D000818:Animals; D011232:Chemical Precipitation; D004195:Disease Models, Animal; D006801:Humans; D019636:Neurodegenerative Diseases / Q000378:metabolism*; D010447:Peptide Hydrolases / Q000378:metabolism; D055503:Protein Multimerization / Q000502:physiology; D011499:Protein Processing, Post-Translational / Q000502:physiology; D016875:tau Proteins / Q000378:metabolism* / Q000502:physiology
chemical_list: D016875:tau Proteins; D010447:Peptide Hydrolases