公开(公告)号：US20190105509A1

公开(公告)日：2019-04-11

申请号：US16135938

申请日：2018-09-19

申请人： Li-Huei Tsai ,  Anthony James Martorell ,  Ho-Jun Suk ,  Ed Boyden

发明人： Li-Huei Tsai ,  Anthony James Martorell ,  Ho-Jun Suk ,  Ed Boyden

IPC分类号： A61N5/06

摘要： Devices, systems, and methods for a treating dementia or Alzheimer's disease in a subject in need thereof. In one example, combined auditory and visual stimuli having a frequency of about 20 Hz to about 60 Hz, and more specifically about 40 Hz, are non-invasively delivered to the subject to induce synchronized gamma oscillations in at least one brain region of the subject. In particular, pursuant to various treatment and exposure protocols, combined auditory and visual stimulation (as opposed to auditory or visual stimulation alone) promotes a microglia response in the medial prefrontal cortex (mPFC). More generally, combined auditory and visual stimulation induces an extended microglia clustering response in the auditory cortex, the visual cortex, and the mPFC.

公开(公告)号：US20170143934A1

公开(公告)日：2017-05-25

申请号：US15360637

申请日：2016-11-23

申请人： Li-Huei Tsai ,  Emery Brown ,  Hannah Iaccarino ,  Anthony James Martorell ,  Chinnakkaruppan Adaikkan

发明人： Li-Huei Tsai ,  Emery Brown ,  Hannah Iaccarino ,  Anthony James Martorell ,  Chinnakkaruppan Adaikkan

IPC分类号： A61M21/00 ,  A61H23/00 ,  A61N5/06

CPC分类号： A61M21/00 ,  A61H23/00 ,  A61M2021/0022 ,  A61M2021/0027 ,  A61M2021/0044 ,  A61N5/062 ,  A61N5/0622 ,  A61N2005/063 ,  A61N2005/0651 ,  A61N2005/0662

摘要： The present disclosure provides systems and methods for at least one of preventing, reducing, and treating a level of or change in at least one of amyloid-β (Aβ) peptide, C-terminal fragment-β (β-CTF), β-secretase (BACE1), γ-secretase, neuroinflammation, and/or dementia (e.g., Alzheimer's disease or age-related decline) in a subject by inducing synchronized gamma oscillations in the brain of the subject using, for example, a stimulus-emitting device to emit a stimulus (e.g., light, sound, and/or haptic) at a frequency (e.g., about 40 Hz) that synchronously activates in vivo a specific cell type (e.g., fast-spiking-parvalbumin (FS-PV) immunoreactive interneurons) and/or brain region (e.g., a sensory cortex and/or hippocampus) of the subject.

公开(公告)号：US20170304584A1

公开(公告)日：2017-10-26

申请号：US15647157

申请日：2017-07-11

申请人： Li-Huei Tsai ,  Emery Brown ,  Hannah Iaccarino ,  Anthony James Martorell ,  Chinnakkaruppan Adaikkan

发明人： Li-Huei Tsai ,  Emery Brown ,  Hannah Iaccarino ,  Anthony James Martorell ,  Chinnakkaruppan Adaikkan

IPC分类号： A61M21/00 ,  A61H23/00 ,  A61N5/06

CPC分类号： A61M21/00 ,  A61H23/00 ,  A61M2021/0022 ,  A61M2021/0027 ,  A61M2021/0044 ,  A61N5/062 ,  A61N5/0622 ,  A61N2005/063 ,  A61N2005/0651 ,  A61N2005/0662

摘要： The present disclosure provides systems and methods for at least one of preventing, reducing, and treating a level of or change in at least one of amyloid-β (Aβ) peptide, C-terminal fragment-β (β-CTF), β-secretase (BACE1), γ-secretase, neuroinflammation, and/or dementia (e.g., Alzheimer's disease or age-related decline) in a subject by inducing synchronized gamma oscillations in the brain of the subject using, for example, a stimulus-emitting device to emit a stimulus (e.g., light, sound, and/or haptic) at a frequency (e.g., about 40 Hz) that synchronously activates in vivo a specific cell type (e.g., fast-spiking-parvalbumin (FS-PV) immunoreactive interneurons) and/or brain region (e.g., a sensory cortex and/or hippocampus) of the subject.

公开(公告)号：US20220151864A1

公开(公告)日：2022-05-19

申请号：US17531616

申请日：2021-11-19

申请人： Li-Huei Tsai ,  Ho-Jun SUK ,  Guojie Xu ,  Arit Banerjee

发明人： Li-Huei Tsai ,  Ho-Jun SUK ,  Guojie Xu ,  Arit Banerjee

IPC分类号： A61H23/00

摘要： A method of treating neurodegeneration in a subject that includes administering a non-invasive tactile stimulus having a stimulus frequency of about 30 Hz to about 50 Hz to a subject to induce synchronized gamma oscillations in at least one portion of the peripheral nervous system of the subject, of the spinal cord of the subject, or both.

公开(公告)号：US09241916B2

公开(公告)日：2016-01-26

申请号：US11955680

申请日：2007-12-13

申请人： David A. Sinclair ,  Li-Huei Tsai ,  Andre Fischer

发明人： David A. Sinclair ,  Li-Huei Tsai ,  Andre Fischer

IPC分类号： A01N37/18 ,  A61K38/00 ,  C07H21/04 ,  A61K31/122 ,  A61K31/015 ,  A61K31/05 ,  A61K31/352 ,  A61K31/415 ,  A61K31/473 ,  A61K31/519

CPC分类号： A61K31/122 ,  A61K31/015 ,  A61K31/05 ,  A61K31/352 ,  A61K31/415 ,  A61K31/473 ,  A61K31/519 ,  G01N2333/98 ,  G01N2800/2814

摘要： Provided herein are methods and compositions for enhancing the cognitive performance of a subject in need thereof. A method may include administering to a subject an agent that increases the level of protein or activity of a sirtuin, such as SIRT1.

摘要翻译： 本文提供用于增强有需要的受试者的认知表现的方法和组合物。 方法可以包括向受试者施用增加沉默调节蛋白（例如SIRT1）的蛋白质或活性水平的试剂。

公开(公告)号：US08841346B2

公开(公告)日：2014-09-23

申请号：US13595048

申请日：2012-08-27

申请人： Li-Huei Tsai ,  Ji-Song Guan ,  Stephen J. Haggarty ,  Edward Holson ,  Florence Wagner ,  Johannes Graeff

发明人： Li-Huei Tsai ,  Ji-Song Guan ,  Stephen J. Haggarty ,  Edward Holson ,  Florence Wagner ,  Johannes Graeff

IPC分类号： A01N37/18 ,  A61K31/16 ,  A61K31/165 ,  A61K31/195 ,  C07C237/42 ,  A61K45/06 ,  A61K31/167

CPC分类号： A61K31/195 ,  A61K31/167 ,  A61K45/06 ,  C07C237/42 ,  A61K2300/00

摘要： The invention relates to methods and compositions for promoting cognitive function and/or treating cognitive function disorders and impairments. In particular the methods are accomplished by administering to a subject CI-994 or dinaline or a pharmaceutically acceptable salt, ester, prodrug or metabolite thereof.

摘要翻译： 本发明涉及用于促进认知功能和/或治疗认知功能障碍和损伤的方法和组合物。 特别地，所述方法通过给予受试者CI-994或迪拉丁胺或其药学上可接受的盐，酯，前药或代谢物来完成。

公开(公告)号：US20110224303A1

公开(公告)日：2011-09-15

申请号：US12917402

申请日：2010-11-01

申请人： Li-Huei Tsai ,  Ji-Song Guan ,  Stephen J. Haggarty ,  Edward Holson ,  Florence Wagner ,  Johannes Graeff

发明人： Li-Huei Tsai ,  Ji-Song Guan ,  Stephen J. Haggarty ,  Edward Holson ,  Florence Wagner ,  Johannes Graeff

IPC分类号： A61K31/167 ,  C07C237/40 ,  A61P25/28 ,  A61P25/00 ,  A61P25/18 ,  A61P25/22 ,  A61P25/30

CPC分类号： A61K31/195 ,  A61K31/167 ,  A61K45/06 ,  C07C237/42 ,  A61K2300/00

摘要： The invention relates to methods and compositions for promoting cognitive function and/or treating cognitive function disorders and impairments. In particular the methods are accomplished by administering to a subject CI-994 or dinaline or a pharmaceutically acceptable salt, ester, prodrug or metabolite thereof.

摘要翻译： 本发明涉及用于促进认知功能和/或治疗认知功能障碍和损伤的方法和组合物。 特别地，所述方法通过给予受试者CI-994或迪拉丁胺或其药学上可接受的盐，酯，前药或代谢物来完成。

公开(公告)号：US07250551B2

公开(公告)日：2007-07-31

申请号：US10625986

申请日：2003-07-24

申请人： Li-Huei Tsai ,  Ming-Sum Lee ,  Jonathan C. Cruz

发明人： Li-Huei Tsai ,  Ming-Sum Lee ,  Jonathan C. Cruz

IPC分类号： A01K67/27 ,  G01N33/00 ,  C12N15/00 ,  C12N5/00

CPC分类号： A01K67/0275 ,  A01K2217/05 ,  A01K2227/105 ,  A01K2267/0318 ,  A61K31/00 ,  A61K31/365 ,  A61K49/0008 ,  C07K2319/41 ,  C07K2319/60 ,  C12N15/8509 ,  C12N2710/16611 ,  C12N2710/16643 ,  C12N2830/00 ,  C12Q1/485 ,  G01N33/6896 ,  G01N2500/04 ,  G01N2800/2821

摘要： Disclosed are improved methods of treating individuals with Alzheimer's disease (AD) as well as methods to diagnose AD in an individual. Also included are compounds and methods of identifying compounds to treat AD. The present invention also discloses methods for decreasing the phosphorylation of amyloid precursor protein (APP), including inhibiting phosphorylation of amino acid residue tyrosine 668 of APP and for reducing cleavage of APP. The present invention further discloses transgenic (Tg), non-human animals and cells expressing a p25 transgene that are models of neurodegenerative diseases. Embodiments of the present invention are directed to methods wherein the Tg animals and Tg cells of the invention are used to screen for modulators of neurodegenerative disorders. The Tg animals and cells of the present invention are useful for elucidating the mechanisms of neurodegenerative disorders.

摘要翻译： 公开了治疗患有阿尔茨海默病（AD）的个体的改进方法以及在个体中诊断AD的方法。 还包括鉴定化合物以治疗AD的化合物和方法。 本发明还公开了降低淀粉样蛋白前体蛋白（APP）的磷酸化的方法，包括抑制APP的氨基酸残基酪氨酸668的磷酸化和减少APP的切割。 本发明还公开了转基因（Tg）非人动物和表达作为神经变性疾病模型的p25转基因的细胞。 本发明的实施方案涉及其中本发明的Tg动物和Tg细胞用于筛选神经变性疾病的调节剂的方法。 本发明的Tg动物和细胞可用于阐明神经变性疾病的机制。

公开(公告)号：US20050261475A1

公开(公告)日：2005-11-24

申请号：US11058735

申请日：2005-02-14

申请人： Huang-Chun Tseng ,  Li-Huei Tsai

发明人： Huang-Chun Tseng ,  Li-Huei Tsai

IPC分类号： C07K1/02 ,  C07K1/13 ,  C07K14/47

CPC分类号： C07K1/13

摘要： One aspect of the present invention relates to a method of labeling a peptide or protein comprising a phosphorylated amino acid comprising: a) removing from the peptide or protein the phosphate group via a β-elimination to form a double bond conjugated to a C═O group; b) reacting the double bond from step a) with a nucleophile comprising a tag on a solid support; and c) removing the solid support from the product of step b) forming the labeled peptide or protein. A second aspect of the invention relates to a solid support comprising a linker and tag between the solid support and a nucleophile, wherein the tag comprises a label.

摘要翻译： 本发明的一个方面涉及标记包含磷酸化氨基酸的肽或蛋白质的方法，包括：a）通过β-消除从肽或蛋白质去除磷酸基团以形成与C-O基团缀合的双键; b）使来自步骤a）的双键与在固体载体上包含标签的亲核试剂反应; 和c）从步骤b）的产物中除去固体支持物，形成标记的肽或蛋白质。 本发明的第二方面涉及一种固体支持物，其包含固体支持物和亲核试剂之间的接头和标签，其中标签包含标签。

公开(公告)号：US20190126062A1

公开(公告)日：2019-05-02

申请号：US16156833

申请日：2018-10-10

申请人： Chinnakkaruppan ADAIKKAN ,  Li-Huei Tsai

发明人： Chinnakkaruppan ADAIKKAN ,  Li-Huei Tsai

IPC分类号： A61N5/06 ,  A61N5/10

摘要： Devices, systems, and methods for treating dementia or Alzheimer's disease in a subject in need thereof. In one example, chronic visual stimuli having a frequency of about 30 Hz to about 50 Hz, and more specifically about 40 Hz, are non-invasively delivered to the subject to entrain gamma oscillations in multiple brain regions of the subject, including the prefrontal cortex (PFC) and the hippocampus. The entrained gamma oscillations modulate neuronal activity across multiple brain regions (e.g., facilitate functional binding of neural networks at low gamma frequencies) to induce various neuroprotective effects (e.g., amelioration of amyloid plaques and tau hyper-phosphorylation) and reduce neurodegeneration. Neuronal activity mediated by the chronic visual stimuli reduces an immune response in microglia and ameliorates aberrantly modified genes and proteins involved in membrane trafficking, intracellular transport, synaptic function, neuroinflammation and DNA damage response. Behavior modification including enhanced learning and memory is observed.