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：US20110009475A1

公开(公告)日：2011-01-13

申请号：US12599518

申请日：2008-07-11

申请人： Andre Fischer ,  Li-Huei Tsai

发明人： Andre Fischer ,  Li-Huei Tsai

IPC分类号： A61K31/365 ,  A61K31/506 ,  A61K31/52 ,  A61K31/7088 ,  A61P25/00

CPC分类号： A61K31/505 ,  A61K31/13 ,  A61K31/365 ,  A61K31/52 ,  A61K31/7076 ,  A61K31/7088 ,  A61K45/06 ,  A61K2300/00

摘要： The invention relates to methods and products for treating emotional disorders such as stress induced emotional disorders, as well as related assays and kits. Methods include administering to a subject an effective amount of an agent for targeting the Rac1, Cdk5, p35, PAK-1 pathway to treat the emotional disorder. The agent for targeting the Rac1, Cdk5, p35, PAK-1 pathway may be, for instance a Rac-1 inhibitor, a Cdk5 inhibitor, a PAK-1 activator, or p35 mobilizing agent.

摘要翻译： 本发明涉及用于治疗情绪障碍如压力诱导的情绪障碍的方法和产品，以及相关的测定和试剂盒。 方法包括向受试者施用有效量的用于靶向Rac1，Cdk5，p35，PAK-1途径以治疗情绪障碍的药剂。 用于靶向Rac1，Cdk5，p35，PAK-1途径的药剂可以是例如Rac-1抑制剂，Cdk5抑制剂，PAK-1激活剂或p35移动剂。

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：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

公开(公告)号：US20080300205A1

公开(公告)日：2008-12-04

申请号：US11998834

申请日：2007-11-30

申请人： Li-Huei Tsai ,  Andre Fischer ,  Stephen Haggarty ,  Weiping Tang

发明人： Li-Huei Tsai ,  Andre Fischer ,  Stephen Haggarty ,  Weiping Tang

IPC分类号： A61K31/7052 ,  A61K31/19 ,  A61K31/215 ,  A61K31/164 ,  A61P25/00 ,  A61K31/4192 ,  A61K31/404 ,  A61K31/7068

CPC分类号： A61K31/164 ,  A61K31/19 ,  A61K31/215 ,  A61K31/404 ,  A61K31/4192 ,  A61K31/7052 ,  A61K31/7068

摘要： The invention relates to methods and products for enhancing and improving recovery of lost memories. In particular the methods are accomplished through the increase of histone acetylation.

摘要翻译： 本发明涉及用于增强和改善丢失记忆恢复的方法和产品。 特别是通过增加组蛋白乙酰化来实现这些方法。

公开(公告)号：US20070185042A1

公开(公告)日：2007-08-09

申请号：US10567537

申请日：2004-08-09

申请人： Li-Huei Tsai ,  Kenneth Kosik

发明人： Li-Huei Tsai ,  Kenneth Kosik

IPC分类号： A61K48/00 ,  C07H21/02 ,  C12N5/08

CPC分类号： C12N15/1137 ,  A61K38/00 ,  C12N2310/111 ,  C12N2310/14

摘要： The present invention relates to siRNA molecules derived from BACE1 and BACE2 genes. Accordingly, provided herein are siRNA molecules comprising a nucleotide sequence consisting essentially of a BACE1 or BACE2 gene. Also provided are methods for reducing the level of BACE1 protein in a cell. Further provided are methods for preparing a pharmaceutical composition comprising an siRNA with a pharmaceutically acceptable carrier.

摘要翻译： 本发明涉及衍生自BACE1和BACE2基因的siRNA分子。 因此，本文提供了包含基本上由BACE1或BACE2基因组成的核苷酸序列的siRNA分子。 还提供了降低细胞中BACE1蛋白水平的方法。 还提供了制备包含具有药学上可接受的载体的siRNA的药物组合物的方法。

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：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：US20050014821A1

公开(公告)日：2005-01-20

申请号：US10625986

申请日：2003-07-24

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

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

IPC分类号： A01K67/027 ,  A61K31/00 ,  A61K31/365 ,  A61K49/00 ,  C12N15/85 ,  C12Q1/48 ,  G01N33/68

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。