2008
DOI: 10.1124/jpet.107.130526
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Abstract: Neurofibrillary tangles composed of aggregated, hyperphosphorylated tau in an abnormal conformation represent one of the major pathological hallmarks of Alzheimer's disease (AD) and other tauopathies. However, recent data suggest that the pathogenic processes leading to cognitive impairment occur before the formation of classic tangles. In the earliest stages of tauopathy, tau detaches from microtubules and accumulates in the cytosol of the somatodendritic compartment of cells. Either as a cause or an effect, … Show more

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Cited by 201 publications
(146 citation statements)
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“…Importantly, targeting tau extends treatment to tau-only dementias, of which there are many. Current strategies in developing tau-directed treatments include inhibition of tau aggregation (34)(35)(36)(37)(38), stabilization of microtubules (39,40), inhibition of kinases (41,42), induction of tau clearance (43)(44)(45), immunotherapy (46), and indirect modulation of tau function (47). So far, however, only a limited number of compounds proved efficacy in tau transgenic mouse models, and even fewer progressed into clinical trials (13).…”
Section: Discussionmentioning
confidence: 99%
“…Importantly, targeting tau extends treatment to tau-only dementias, of which there are many. Current strategies in developing tau-directed treatments include inhibition of tau aggregation (34)(35)(36)(37)(38), stabilization of microtubules (39,40), inhibition of kinases (41,42), induction of tau clearance (43)(44)(45), immunotherapy (46), and indirect modulation of tau function (47). So far, however, only a limited number of compounds proved efficacy in tau transgenic mouse models, and even fewer progressed into clinical trials (13).…”
Section: Discussionmentioning
confidence: 99%
“…222 Other microtubule-stabilizing approaches are reviewed by Michelis et al 223,224 The neuronal tubulin-preferring agent NAP was reported to display less side effects than the non-cell-typespecific taxol, which inhibits cell mitosis in general. 225 The octapeptide NAPVSIPQ (NAP) has a preference for neuronal tubulin and crosses the BBB readily when administered intranasally. Continuous NAP treatment of a triple transgenic mouse model characterized by A␤ and tau-based pathology reduced the levels of hyperphosphorylated soluble and insoluble tau and enhanced the cognitive function of these mice.…”
Section: Microtubule-stabilizing Drugsmentioning
confidence: 99%
“…Continuous NAP treatment of a triple transgenic mouse model characterized by A␤ and tau-based pathology reduced the levels of hyperphosphorylated soluble and insoluble tau and enhanced the cognitive function of these mice. 85,225 …”
Section: Microtubule-stabilizing Drugsmentioning
confidence: 99%
“…TFP5 was designed to inhibit Cdk5/p25 activity and tau hyperphosphorylation, yet its administration to the 5XFAD mice by intraperitoneal (IP) injection not only reduced the phosphorylation of tau and neurofilaments, but also decreased Aβ accumulation and neuroinflammation in the brains of these mice [22]. Intranasally administered NAP, an octapeptide promoting microtubule assembly, reduced both Aβ accumulation and tau hyperphosphorylation in the 3xTg AD mice [29,30]. Amyloidopathy and tauopathy might be more complicated and correlated than previously thought.…”
Section: Other Designed Anti-ad Peptidesmentioning
confidence: 99%