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Tau Phosphorylation and Aggregation as a Therapeutic Target in Tauopathies

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Tauopathies are neurodegenerative diseases characterized by insoluble hyperphosphorylated deposits of the microtubuleassociated protein tau in the central nervous system. In these disorders, tau is believed to cause neurodegeneration and neuronal loss due to the loss of function of the normal protein, and/or the gain of toxic properties by generating multimeric species. The obstacles found in amyloid-based therapies in Alzheimer's disease, the most common tauopathy, have stimulated the search for alternative targets, including tau. In this article, we review the strategies aimed at reducing tau phosphorylation and aggregation as a target for drug intervention in tauopathies.

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Keywords: AZD1080; Alzheimer; Alzheimer's disease; Down syndrome; FTLD; MMSE; NAPVSIPQ; Niemann-Pick disease type C; SB216763; SMaRT technology; Tau; alsterpaullone; aminothienopyridazines; anthraquinones; argyrophilic grain disease; chloroquine; chronic traumatic encephalopathy; corticobasal degeneration; corticobasal syndrome; dementia; frontotemporal dementia; frontotemporal lobar degeneration; glycation; glycosylation; immunization; kinase inhibitors; multiphoton microscopy; nitration; nitrosylation; phenothiazines; phenyl thiazolylhydrazide benzofuran; phosphorylation; polyamination; polyphenols; porphyrins; post-encephalitic parkinsonism; postencephalitic parkinsonism; progressive supranuclear palsy; pyrimidotriazines; quinoxaline; sumoylation; tau fibrillization; tauopathies; truncation; ubiquitination

Document Type: Research Article

Publication date: 2010-12-01

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  • CNS & Neurological Disorders - Drug Targets aims to cover all the latest and outstanding developments on the medicinal chemistry, pharmacology, molecular biology, genomics and biochemistry of contemporary molecular targets involved in neurological and central nervous system (CNS) disorders e.g. disease specific proteins, receptors, enzymes, genes. Each issue of the journal will contain a series of timely in-depth reviews written by leaders in the field covering a range of current topics on drug targets involved in neurological and CNS disorders. As the discovery, identification, characterization and validation of novel human drug targets for neurological and CNS drug discovery continues to grow; this journal will be essential reading for all pharmaceutical scientists involved in drug discovery and development.
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