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Current Alzheimer Research 2011, Vol. 8 (6) :659 -665 <<-上一篇 下一篇 ->>
Tau Oligomers as Potential Targets for Immunotherapy for Alzheimer's;Disease and Tauopathies
Lasagna-Reeves, C. A.;Castillo-Carranza, D. L.;Jackson, G. R.;Kayed, R.
[Lasagna-Reeves, C. A.; Castillo-Carranza, D. L.; Jackson, G. R.; Kayed, R.] Univ Texas Med Branch, Dept Neurol, George P & Cynthia Woods Mitchell Ctr Neurodegene, Galveston, TX 77555 USA.
Abstract: The aggregation and accumulation of the microtubule-associated protein (Tau) is a pathological hallmark of Alzheimer disease (AD) and many neurodegenerative diseases. For a long time research has focused on neurofibrillary tangles (NFTs) and other large meta-stable inclusions composed of aggregated hyperphosphorylated tau protein. The correlation between these structures and disease progression produced conflicting results; moreover, the mechanism of their formation remains poorly understood. Lately, the significance and toxicity of NFTs have been challenged and a new aggregated tau entity has emerged as the true pathogenic species in tauopathies and a possible mediator of A beta toxicity in AD; specifically, aggregates of a size intermediate between monomers and NFTs the so-called tau oligomers. Tremendous efforts have been devoted toward the optimization of a safe vaccine for AD by targeting A beta peptide; despite the disappointing results, these studies produced a wealth of useful knowledge, which should be considered in developing tau-based immunotherapy. Herein, we discuss the evidence supporting the critical role of tau oligomers in AD, the potential and challenges for targeting them by immunotherapy as a novel approach for AD treatment.
Keywords: PROTEIN-TAU TRANSGENIC MICE CASPASE-CLEAVAGE NEURODEGENERATIVE DISORDERS MODEL MOUSE NEUROFIBRILLARY TANGLES A-BETA OLIGOMERS CENTRAL-NERVOUS-SYSTEM SOLUBLE AMYLOID OLIGOMERS PAIRED HELICAL FILAMENTS
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