Intracellular accumulation of tau protein is a hallmark of Alzheimer's Disease and Progressive Supranuclear Palsy, as well as other neurodegenerative disorders collectively known as tauopathies. Despite our increasing understanding of the mechanisms leading to the initiation and progression of tau pathology, the field still lacks appropriate disease models to facilitate drug discovery. Here, we established a novel and modulatable seeding-based neuronal model of full-length 4R tau accumulation using humanized mouse cortical neurons and seeds from P301S human tau transgenic animals.
View Article and Find Full Text PDFTrace Amine-Associated Receptor 1 (TAAR1) is a potential target for the treatment of depression and other CNS disorders. However, the precise functional roles of TAAR1 to the actions of clinically used antidepressants remains unclear. Herein, we addressed these issues employing the TAAR1 agonist, o-phenyl-iodotyramine (o-PIT), together with TAAR1-knockout (KO) mice.
View Article and Find Full Text PDFJ Pharmacol Exp Ther
February 2008
The novel benzopyranopyrrolidine, S33138 [N-[4-[2-[(3aS,9bR)-8-cyano-1,3a,4,9b-tetrahydro[1]benzopyrano[3,4-c]pyrrol-2(3H)-yl)-ethyl]phenylacetamide], is a preferential antagonist of cloned human D(3) versus D(2L) and D(2S) receptors. In mice, S33138 (0.04-2.
View Article and Find Full Text PDFThough dopaminergic mechanisms modulate cholinergic transmission and cognitive function, the significance of specific receptor subtypes remains uncertain. Here, we examined the roles of dopamine D(3) versus D(2) receptors. By analogy with tacrine (0.
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