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Full-Text Articles in Neurosciences
Assessment Of The Effects Of Mptp And Paraquat On Dopaminergic Neurons And Microglia In The Substantia Nigra Pars Compacta Of C57bl/6 Mice., Richard Jay Smeyne, Charles B. Breckenridge, Melissa Beck, Yun Jiao, Mark T. Butt, Jeffrey C. Wolf, Dan Zadory, Daniel J. Minnema, Nicholas C. Sturgess, Kim Z. Travis, Andrew R. Cook, Lewis L. Smith, Philip A. Botham
Assessment Of The Effects Of Mptp And Paraquat On Dopaminergic Neurons And Microglia In The Substantia Nigra Pars Compacta Of C57bl/6 Mice., Richard Jay Smeyne, Charles B. Breckenridge, Melissa Beck, Yun Jiao, Mark T. Butt, Jeffrey C. Wolf, Dan Zadory, Daniel J. Minnema, Nicholas C. Sturgess, Kim Z. Travis, Andrew R. Cook, Lewis L. Smith, Philip A. Botham
Department of Neuroscience Faculty Papers
The neurotoxicity of paraquat dichloride (PQ) was assessed in two inbred strains of 9- or 16-week old male C57BL/6 mice housed in two different laboratories and compared to the effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). PQ was administered by intraperitoneal injections; either once (20 mg/kg) or twice (10 mg/kg) weekly for 3 weeks, while MPTP-HCl was injected 4 times on a single day (20 mg/kg/dose). Brains were collected 8, 16, 24, 48, 96 or 168 hours after the last PQ treatment, and 48 or 168 hours after MPTP treatment. Dopamine neurons in the substantia nigra pars compacta (SNpc) were identified by antibodies …
Tau Phosphorylation At Alzheimer's Disease-Related Ser356 Contributes To Tau Stabilization When Par-1/Mark Activity Is Elevated., Kanae Ando, Mikiko Oka, Yosuke Ohtake, Motoki Hayashishita, Sawako Shimizu, Shin-Ichi Hisanaga, Koichi M. Iijima
Tau Phosphorylation At Alzheimer's Disease-Related Ser356 Contributes To Tau Stabilization When Par-1/Mark Activity Is Elevated., Kanae Ando, Mikiko Oka, Yosuke Ohtake, Motoki Hayashishita, Sawako Shimizu, Shin-Ichi Hisanaga, Koichi M. Iijima
Department of Neuroscience Faculty Papers
Abnormal phosphorylation of the microtubule-associated protein tau is observed in many neurodegenerative diseases, including Alzheimer's disease (AD). AD-related phosphorylation of two tau residues, Ser262 and Ser356, by PAR-1/MARK stabilizes tau in the initial phase of mismetabolism, leading to subsequent phosphorylation events, accumulation, and toxicity. However, the relative contribution of phosphorylation at each of these sites to tau stabilization has not yet been elucidated. In a Drosophila model of human tau toxicity, we found that tau was phosphorylated at Ser262, but not at Ser356, and that blocking Ser262 phosphorylation decreased total tau levels. By contrast, when PAR-1 was co-overexpressed with tau, …
Closed-State Inactivation Involving An Internal Gate In Kv4.1 Channels Modulates Pore Blockade By Intracellular Quaternary Ammonium Ions., Jeffrey D. Fineberg, Tibor G. Szanto, Gyorgy Panyi, Manuel Covarrubias
Closed-State Inactivation Involving An Internal Gate In Kv4.1 Channels Modulates Pore Blockade By Intracellular Quaternary Ammonium Ions., Jeffrey D. Fineberg, Tibor G. Szanto, Gyorgy Panyi, Manuel Covarrubias
Department of Neuroscience Faculty Papers
Voltage-gated K(+) (Kv) channel activation depends on interactions between voltage sensors and an intracellular activation gate that controls access to a central pore cavity. Here, we hypothesize that this gate is additionally responsible for closed-state inactivation (CSI) in Kv4.x channels. These Kv channels undergo CSI by a mechanism that is still poorly understood. To test the hypothesis, we deduced the state of the Kv4.1 channel intracellular gate by exploiting the trap-door paradigm of pore blockade by internally applied quaternary ammonium (QA) ions exhibiting slow blocking kinetics and high-affinity for a blocking site. We found that inactivation gating seemingly traps benzyl-tributylammonium …
Stabilization Of Microtubule-Unbound Tau Via Tau Phosphorylation At Ser262/356 By Par-1/Mark Contributes To Augmentation Of Ad-Related Phosphorylation And Aβ42-Induced Tau Toxicity., Kanae Iijima-Ando, Akiko Maruko-Otake, Yosuke Ohtake, Motoki Hayashishita, Michiko Sekiya, Koichi M Iijima
Stabilization Of Microtubule-Unbound Tau Via Tau Phosphorylation At Ser262/356 By Par-1/Mark Contributes To Augmentation Of Ad-Related Phosphorylation And Aβ42-Induced Tau Toxicity., Kanae Iijima-Ando, Akiko Maruko-Otake, Yosuke Ohtake, Motoki Hayashishita, Michiko Sekiya, Koichi M Iijima
Department of Neuroscience Faculty Papers
Abnormal accumulation of the microtubule-interacting protein tau is associated with neurodegenerative diseases including Alzheimer's disease (AD). β-amyloid (Aβ) lies upstream of abnormal tau behavior, including detachment from microtubules, phosphorylation at several disease-specific sites, and self-aggregation into toxic tau species in AD brains. To prevent the cascade of events leading to neurodegeneration in AD, it is essential to elucidate the mechanisms underlying the initial events of tau mismetabolism. Currently, however, these mechanisms remain unclear. In this study, using transgenic Drosophila co-expressing human tau and Aβ, we found that tau phosphorylation at AD-related Ser262/356 stabilized microtubule-unbound tau in the early phase of …