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Götz J, Ittner A, Ittner LM. Tau-targeted treatment strategies in Alzheimer’s disease. Br J Pharmacol 165: 1246-1259

Alzheimer's and Parkinson's Disease Laboratory, Brain & Mind Research Institute, University of Sydney, Camperdown, NSW, Australia.
British Journal of Pharmacology (Impact Factor: 4.99). 11/2011; 165(5):1246-59. DOI: 10.1111/j.1476-5381.2011.01713.x
Source: PubMed

ABSTRACT With populations ageing worldwide, the need for treating and preventing diseases associated with high age is pertinent. Alzheimer's disease (AD) is reaching epidemic proportions, yet the currently available therapies are limited to a symptomatic relief, without halting the degenerative process that characterizes the AD brain. As in AD cholinergic neurons are lost at high numbers, the initial strategies were limited to the development of acetylcholinesterase inhibitors, and more recently the NMDA receptor antagonist memantine, in counteracting excitotoxicity. With the identification of the protein tau in intracellular neurofibrillary tangles and of the peptide amyloid-β (Aβ) in extracellular amyloid plaques in the AD brain, and a better understanding of their role in disease, newer strategies are emerging, which aim at either preventing their formation and deposition or at accelerating their clearance. Interestingly, what is well established to combat viral diseases in peripheral organs - vaccination - seems to work for the brain as well. Accordingly, immunization strategies targeting Aβ show efficacy in mice and to some degree also in humans. Even more surprising is the finding in mice that immunization strategies targeting tau, a protein that forms aggregates in nerve cells, ameliorates the tau-associated pathology. We are reviewing the literature and discuss what can be expected regarding the translation into clinical practice and how the findings can be extended to other neurodegenerative diseases with protein aggregation in brain.

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    • "The biochemical commonalities between T2DM and AD would imply that common treatment strategies could be pursued. Among the potentially suitable strategies are vaccinations that have been successful in mice, targeting both Aβ and tau (Götz et al., 2012). Unfortunately, the clinical trials using anti-Aβ antibodies basically failed to meet their primary end points (Karran, 2012), while tau-based strategies have not yet been tested in a clinical setting. "
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    ABSTRACT: The amyloidogenic peptide Aβ plays a key role in Alzheimer's disease (AD) forming insoluble aggregates in the brain. The peptide shares its amyloidogenic properties with amylin that forms aggregates in the pancreas of patients with Type 2 Diabetes mellitus (T2DM). While epidemiological studies establish a link between these two diseases, it is becoming increasingly clear that they also share biochemical features suggesting common pathogenic mechanisms. We discuss commonalities as to how Aβ and amylin deregulate the cellular proteome, how they impair mitochondrial functions, to which receptors they bind, aspects of their clearance and how therapeutic strategies exploit the commonalities between Aβ and amylin. We conclude that research into these two molecules is mutually beneficial for the treatment of AD and T2DM.
    Frontiers in Aging Neuroscience 08/2013; 5:38. DOI:10.3389/fnagi.2013.00038 · 2.84 Impact Factor
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    • "Adv Exp Med Biol 740 , 1193 - 1217 . [ 117 ] Lim YA , Giese M , Shepherd C , Halliday G , Kobayashi M , Takamatsu K , Staufenbiel M , Eckert A , Gotz J ( 2012 ) Role of hippocalcin in mediating Abeta toxicity . Biochim Biophys Acta 1822 , 1247 - 1257 . "
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    • "Adv Exp Med Biol 740 , 1193 - 1217 . [ 117 ] Lim YA , Giese M , Shepherd C , Halliday G , Kobayashi M , Takamatsu K , Staufenbiel M , Eckert A , Gotz J ( 2012 ) Role of hippocalcin in mediating Abeta toxicity . Biochim Biophys Acta 1822 , 1247 - 1257 . "
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