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.

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：US08263547B2

公开(公告)日：2012-09-11

申请号：US12474229

申请日：2009-05-28

申请人： Li-Huei Tsai ,  Yingwei Mao ,  Jon Madison ,  Stephen J. Haggarty

发明人： Li-Huei Tsai ,  Yingwei Mao ,  Jon Madison ,  Stephen J. Haggarty

IPC分类号： A61K38/00 ,  C07K5/00 ,  G01N33/53 ,  C12Q1/00

CPC分类号： A61K38/1709 ,  A61K31/00 ,  A61K31/351 ,  A61K31/40

摘要： The invention relates to methods of treating neurological disorders in a subject, by activating a DISC1 pathway. Methods of promoting neurogenesis in adult neural progenitor cells, enhancing nerve generation and treating GSK3 disorders as well as related compositions are also provided.

摘要翻译： 本发明涉及通过激活DISC1途径治疗受试者神经障碍的方法。 还提供了促进成年神经祖细胞神经发生，增强神经产生和治疗GSK3疾病以及相关组合物的方法。

公开(公告)号：US20060025337A1

公开(公告)日：2006-02-02

申请号：US11074374

申请日：2005-03-07

申请人： David Sinclair ,  Li-Huei Tsai ,  Minh Nguyen ,  Konrad Howitz ,  Robert Zipkin ,  Kevin Bitterman

发明人： David Sinclair ,  Li-Huei Tsai ,  Minh Nguyen ,  Konrad Howitz ,  Robert Zipkin ,  Kevin Bitterman

IPC分类号： A61K38/17 ,  A61K48/00 ,  C12Q1/02

CPC分类号： C12Q1/34 ,  A61K31/00 ,  A61K31/015 ,  A61K31/122 ,  G01N33/6896 ,  G01N2500/00 ,  G01N2800/28 ,  G01N2800/2821

摘要： Provided herein are methods and compositions for modulating the activity of sirtuin deacetylase protein family members; p53 activity; apoptosis; lifespan and sensitivity to stress of cells and organisms. Exemplary methods comprise contacting a cell with an activating compound, such as a flavone, stilbene, flavanone, isoflavone, catechin, chalcone, tannin or anthocyanidin; or an inhibitory compound, such as a sphingolipid, e.g., sphingosine. Also disclosed herein are methods for treating, preventing or diagnosing a disease associated with neuronal cell death, e.g., a neurodegenerative disease.

摘要翻译： 本文提供了调节沉默调节蛋白脱乙酰酶蛋白家族成员的活性的方法和组合物; p53活性; 凋亡; 寿命和对细胞和生物体的压力的敏感性。 示例性方法包括使细胞与活化化合物如黄酮，芪，黄酮酮，异黄酮，儿茶素，查耳酮，单宁或花色素接触; 或抑制性化合物，例如鞘脂，例如鞘氨醇。 本文还公开了用于治疗，预防或诊断与神经元细胞死亡相关的疾病，例如神经变性疾病的方法。

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：US20090111733A1

公开(公告)日：2009-04-30

申请号：US11996028

申请日：2006-07-19

申请人： Sang Ki Park ,  Li-Huei Tsai ,  Yang Shi

发明人： Sang Ki Park ,  Li-Huei Tsai ,  Yang Shi

IPC分类号： A61K38/00 ,  G01N33/50 ,  G01N33/68 ,  A61K31/7088 ,  A61K31/22 ,  A61K31/195 ,  A61K31/19 ,  A61K31/192 ,  A61K31/221 ,  A61P25/00 ,  C07K2/00 ,  A01K67/00

CPC分类号： C12N15/1138 ,  C07K14/705 ,  C07K14/70571 ,  C12N2310/14 ,  G01N33/6896 ,  G01N33/9413 ,  G01N2500/02 ,  G01N2800/304

摘要： Provided herein are methods and compositions for treating or preventing mood disorders and certain other mental disorders. Methods may comprise increasing PAR-4 levels or activity and/or the interaction between PAR-4 and the dopamine (D2) receptor

摘要翻译： 本文提供了用于治疗或预防情绪障碍和某些其它精神障碍的方法和组合物。 方法可包括增加PAR-4水平或活性和/或PAR-4与多巴胺（D2）受体之间的相互作用

公开(公告)号：US20080194803A1

公开(公告)日：2008-08-14

申请号：US11955680

申请日：2007-12-13

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

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

IPC分类号： C07H21/04 ,  C07D471/04

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： 本文提供了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：US20220411751A1

公开(公告)日：2022-12-29

申请号：US17778270

申请日：2020-11-20

申请人： Oleg BUTOVSKY ,  Vladimir LITVAK ,  William RALVENIUS ,  Li-Huei TSAI ,  The Brigham and Women's Hospital, Inc. ,  University of Massachusetts ,  Massachusetts Institute of Technology

发明人： Oleg Butovsky ,  Vladimir Litvak ,  William Ralvenius ,  Li-Huei Tsai

IPC分类号： C12N5/079 ,  A61K35/30

摘要： Provided herein are methods for obtaining populations of reprogrammed MO-homeostatic tolerogenic microglial cells. The methods include providing an initial population of monocytes, e.g., peripheral blood monocytes (PBMC), from a subject, and reprogramming the cells by maintaining the PBMC in culture ex vivo in the presence of a sufficient amount of transforming growth factor-beta (TGFβ) and interferon-gamma (IFNγ) for a time and under conditions sufficient for the cells to become M0-homeostatic tolerogenic microglia. Also provided are methods of use of these cells, e.g., for the treatment of neurodegenerative diseases associated with inflammation, e.g., Alzheimer's Disease (AD); Multiple Sclerosis (MS), e.g., progressive MS; and Amyotrophic Lateral Sclerosis