title: Therapeutic strategies for tau mediated neurodegeneration.
abstract: Based on the amyloid hypothesis, controlling β-amyloid protein (Aβ) accumulation is supposed to suppress downstream pathological events, tau accumulation, neurodegeneration and cognitive decline. However, in recent clinical trials, Aβ removal or reducing Aβ production has shown limited efficacy. Moreover, while active immunisation with Aβ resulted in the clearance of Aβ, it did not prevent tau pathology or neurodegeneration. This prompts the concern that it might be too late to employ Aβ targeting therapies once tau mediated neurodegeneration has occurred. Therefore, it is timely and very important to develop tau directed therapies. The pathomechanisms of tau mediated neurodegeneration are unclear but hyperphosphorylation, oligomerisation, fibrillisation and propagation of tau pathology have been proposed as the likely pathological processes that induce loss of function or gain of toxic function of tau, causing neurodegeneration. Here we review the strategies for tau directed treatments based on recent progress in research on tau and our understanding of the pathomechanisms of tau mediated neurodegeneration.
authors.affiliation: Department of Neurology, Chiba East National Hospital, 673 Nitona, Chuo Ward, Chiba, Chiba 260-8712, Japan. neuroyy@cehpnet.com
authors.forename: Yasumasa
authors.initials: Y
authors.lastname: Yoshiyama
authors.forename: Virginia M Y
authors.initials: VM
authors.lastname: Lee
authors.forename: John Q
authors.initials: JQ
authors.lastname: Trojanowski
mesh_terms: D000544:Alzheimer Disease / Q000628:therapy; D016229:Amyloid beta-Peptides / Q000134:cerebrospinal fluid; D000818:Animals; D015415:Biomarkers; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D007114:Immunization; D007249:Inflammation / Q000188:drug therapy / Q000473:pathology; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000134:cerebrospinal fluid / Q000628:therapy*; D016874:Neurofibrillary Tangles / Q000187:drug effects; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D057165:Proteostasis Deficiencies / Q000188:drug therapy / Q000473:pathology; D051076:Proto-Oncogene Proteins c-fyn / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D016875:tau Proteins / Q000276:immunology / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D015415:Biomarkers; D008869:Microtubule-Associated Proteins; D016875:tau Proteins; D051076:Proto-Oncogene Proteins c-fyn; D010744:Phosphoric Monoester Hydrolases
keywords: Alzheimer's Disease