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1. 发明授权

US06080582A Cell tests for Alzheimer's disease 失效
公开(公告)号：US06080582A
公开(公告)日：2000-06-27
申请号：US79347
申请日：1998-05-15
申请人： Daniel L. Alkon , Rene Etcheberrigaray , Christopher S. Kim , Yi-Fan Han , Tom J. Nelson
发明人： Daniel L. Alkon , Rene Etcheberrigaray , Christopher S. Kim , Yi-Fan Han , Tom J. Nelson
IPC分类号： G01N33/53 , C07K14/47 , C07K16/18 , C12N15/02 , C12P21/08 , C12R1/91 , G01N33/50 , G01N33/531 , G01N33/573 , G01N33/577 , G01N33/68 , A61K38/00 , C07K16/00
CPC分类号： G01N33/5091 , C07K14/4711 , C07K16/18 , G01N33/573 , G01N33/6872 , G01N33/6896 , G01N2333/9121 , G01N2800/2821
摘要： The present invention provides methods for the diagnosis of Alzheimer's disease using human cells. Specifically, one method detects differences between potassium channels in cells from Alzheimer's patient and normal donors, and differences in intracellular calcium concentrations between Alzheimer's and normal cells in response to chemicals known to increase intracellular calcium levels. Other methods detect differences between the memory associated GTP binding Cp20 protein levels between Alzheimer's and normal cells.

2. 发明授权

US5976816A Cell tests for alzheimer's disease 失效
标题翻译：阿尔茨海默病细胞检测
公开(公告)号：US5976816A
公开(公告)日：1999-11-02
申请号：US312202
申请日：1994-09-26
申请人： Daniel L. Alkon , Rene Etcheberrigaray , Christopher S. Kim , Yi-Fan Han , Tom J. Nelson
发明人： Daniel L. Alkon , Rene Etcheberrigaray , Christopher S. Kim , Yi-Fan Han , Tom J. Nelson
IPC分类号： G01N33/53 , C07K14/47 , C07K16/18 , C12N15/02 , C12P21/08 , C12R1/91 , G01N33/50 , G01N33/531 , G01N33/573 , G01N33/577 , G01N33/68 , G01N33/567 , C07K16/00
CPC分类号： G01N33/5091 , C07K14/4711 , C07K16/18 , G01N33/573 , G01N33/6872 , G01N33/6896 , G01N2333/9121 , G01N2800/2821
摘要： The present invention provides methods for the diagnosis of Alzheimer's disease using human cells. Specifically, one method detects differences between potassium channels in cells from Alzheimer's patient and normal donors, and differences in intracellular calcium concentrations between Alzheimer's and normal cells in response to chemicals known to increase intracellular calcium levels. Other methods detect differences between the memory associated GTP binding Cp20 protein levels between Alzheimer's and normal cells.
摘要翻译：本发明提供了使用人类细胞诊断阿尔茨海默病的方法。具体来说，一种方法检测来自阿尔茨海默病患者和正常供体的细胞中的钾通道之间的差异，以及响应于已知增加细胞内钙水平的化学物质的阿尔茨海默氏病和正常细胞之间的细胞内钙浓度的差异。其他方法检测与老年痴呆和正常细胞之间记忆相关的GTP结合Cp20蛋白水平之间的差异。

3. 发明申请

US20110196028A1 PCK ACTIVATION AS A MEANS FOR ENHANCING sAPPa SECRETION AND IMPROVING COGNITION USING BRYOSTATIN TYPE COMPOUNDS 审中-公开
标题翻译： PCK活化作为增强sAPPa分泌和改善使用BRYOSTATIN型化合物的认知的手段
公开(公告)号：US20110196028A1
公开(公告)日：2011-08-11
申请号：US12817642
申请日：2010-06-17
申请人： Rene Etcheberrigaray , Daniel L. Alkon
发明人： Rene Etcheberrigaray , Daniel L. Alkon
IPC分类号： A61K31/365 , A61P25/28 , A61P25/16
CPC分类号： A61K31/7048 , A61K31/00 , A61K31/365
摘要： This invention provides a method for isolating and identifying proteins participating in protein-protein interactions in a complex mixture. The method uses a chemically reactive supporting matrix to isolate proteins that in turn non-covalently bind other proteins. The supporting matrix is isolated, and the non-covalently bound proteins are subsequently released for analysis. Because the proteins are accessible to chemical manipulation at both the binding and release steps, identification of the non-covalently bound proteins yields information on specific classes of interacting proteins, such as calcium-dependent or substrate-dependent protein interactions. This permits selection of a subpopulation of proteins from a complex mixture on the basis of specified interaction criteria. The method has the advantage of screening the entire proteome simultaneously, unlike two-hybrid systems or phage display methods which can only detect proteins binding to a single bait protein at a time. The method is applicable to the study of protein-protein interactions in biopsy and autopsy specimens, to the study of protein-protein interactions in the presence of signaling molecules, pharmacological agents or toxins, and for comparison of diseased and normal tissues or cancerous and untransformed cells.
摘要翻译：本发明提供了一种在复杂混合物中分离和鉴定参与蛋白质 - 蛋白质相互作用的蛋白质的方法。该方法使用化学反应性支持基质来分离蛋白质，而蛋白质又与其它蛋白质非共价结合。分离支持基质，随后释放非共价结合的蛋白质进行分析。因为蛋白质可以在结合和释放步骤中进行化学操作，所以鉴定非共价结合的蛋白质可产生关于相关蛋白质的特定类别的信息，例如钙依赖性或底物依赖性蛋白质相互作用。这允许基于指定的相互作用标准从复杂混合物中选择蛋白质亚群。该方法具有同时筛选整个蛋白质组的优点，不同于双杂交系统或噬菌体展示方法，其一次只能检测到与单个诱饵蛋白结合的蛋白质。该方法适用于活检和尸检标本中蛋白质 - 蛋白质相互作用的研究，在信号分子，药理学试剂或毒素存在下蛋白质 - 蛋白质相互作用的研究，以及用于比较患病和正常组织或癌和未转化的蛋白质 - 蛋白质相互作用细胞。

4. 发明授权

US5580748A Diagnostic tests for alzheimers disease 失效
标题翻译：阿尔茨海默病的诊断试验
公开(公告)号：US5580748A
公开(公告)日：1996-12-03
申请号：US56456
申请日：1993-05-03
申请人： Daniel L. Alkon , Rene Etcheberrigaray , Etsuro Ito , Gary E. Gibson
发明人： Daniel L. Alkon , Rene Etcheberrigaray , Etsuro Ito , Gary E. Gibson
IPC分类号： C07K14/47 , C07K16/18 , G01N33/50 , G01N33/68 , C12Q1/02 , C12Q1/00
CPC分类号： G01N33/6872 , C07K14/4711 , C07K16/18 , G01N33/5091 , G01N33/6896 , G01N2800/2821 , Y10S436/811
摘要： The present invention is a method for the diagnosis of Alzheimer's disease using human cells. Specifically, the method detects differences between potassium channels in cells from Alzheimer's patient and normal donors, and differences in intracellular calcium concentrations between Alzheimer's and normal cells in response to chemicals known to increase intracellular calcium levels.
摘要翻译：本发明是使用人细胞诊断阿尔茨海默氏病的方法。具体地，该方法检测来自阿尔茨海默病患者和正常供体的细胞中的钾通道之间的差异，以及响应于已知增加细胞内钙水平的化学物质的阿尔茨海默氏症和正常细胞之间的细胞内钙浓度的差异。

5. 发明申请

US20130072550A1 PKC ACTIVATION AS A MEANS FOR ENHANCING sAPPalpha SECRETION AND IMROVING COGNITION USING BRYOSTATIN TYPE COMPOUNDS 审中-公开
标题翻译： PKC激活作为增强sAPPalpha分泌和使用BRYOSTATIN型化合物的感染的手段
公开(公告)号：US20130072550A1
公开(公告)日：2013-03-21
申请号：US13608874
申请日：2012-09-10
申请人： Rene Etcheberrigaray , Daniel L. Alkon
发明人： Rene Etcheberrigaray , Daniel L. Alkon
IPC分类号： A61K31/365 , A61P25/28 , A61P25/00
CPC分类号： A61K31/7048 , A61K31/00 , A61K31/365
摘要： The present disclosure relates to methods of administering compounds for treating conditions associated with amyloid processing such as Alzheimer's Disease. Methods are disclosed comprising the step of administering a macrocyclic lactone, a benzolactam, a pyrrolidinone or a combination thereof to a subject in need in an amount effective to decrease soluble Aβ-40 or Aβ-42, or to lower total amyloid precursor protein (“APP”). Methods are also disclosed further comprising the step of identifying a subject with increased soluble Aβ-40 or Aβ-42 levels, or elevated APP levels compared to a control population.
摘要翻译：本公开涉及施用用于治疗与淀粉样蛋白加工如阿尔茨海默病相关的病症的化合物的方法。公开的方法包括将大环内酯，苯并内酰胺，吡咯烷酮或其组合施用于需要的受试者以有效降低可溶性Aβ-40或A-bgr--42的量或降低总淀粉样蛋白前体蛋白（APP）。还公开了进一步包括以下步骤：与对照群体相比，鉴定具有增加的可溶性A-Bgr--40或A＆bgr--42水平或升高的APP水平的受试者的步骤。

6. 发明授权

US06825229B2 Methods for Alzheimer's Disease treatment and cognitive enhancement 有权
标题翻译：阿尔茨海默病治疗和认知增强方法
公开(公告)号：US06825229B2
公开(公告)日：2004-11-30
申请号：US10167491
申请日：2002-06-13
申请人： Rene Etcheberrigaray , Daniel L. Alkon
发明人： Rene Etcheberrigaray , Daniel L. Alkon
IPC分类号： A61K3135
CPC分类号： A61K31/365 , A61K9/0053 , A61K31/00 , A61K31/366 , Y02A50/406
摘要： The present invention relates to compositions and methods to modulate &agr;-secretase and/or to improve cognitive ability. The invention further relates the improved/enhanced cognitive ability in diseased individuals, particularly Alzheimer's Disease patients, and treatment thereof through increased sAPP production. Macrocyclic lactones (i.e. bryostatin class and neristatin class) are compounds preferred for use with the present composition. The present invention also provides methods for increasing the generation of non-amyloidogenic soluble APP comprising the activation of protein kinase C (PKC) by administering an effective amount of PKC activator(s).
摘要翻译：本发明涉及调节α-分泌酶和/或提高认知能力的组合物和方法。本发明进一步涉及改善/增强的患病个体，特别是阿尔茨海默病患者的认知能力，以及通过增加的sAPP产生来治疗它们。大环内酯（即苔藓抑制素类和神经抑制素类）是优选用于本发明组合物的化合物。本发明还提供了通过施用有效量的PKC激活剂来增加包含蛋白激酶C（PKC）的活化的非淀粉样蛋白可溶性APP的产生的方法。

7. 发明申请

US20180217163A1 TREATMENT OF NEURODEGENERATIVE CONDITIONS USING PKC ACTIVATORS AFTER DETERMINING THE PRESENCE OF THE APOE4 ALLELE 审中-公开
公开(公告)号：US20180217163A1
公开(公告)日：2018-08-02
申请号：US15572946
申请日：2016-05-11
申请人： Daniel L. ALKON
发明人： Daniel L. Alkon , Abhik Sen , Thomas Nelson
IPC分类号： G01N33/68 , A61K31/365 , C12Q1/6883 , A61P25/28
CPC分类号： G01N33/6896 , A61K31/365 , A61P25/28 , C12Q1/68 , C12Q1/6883 , C12Q2600/106 , C12Q2600/156 , G01N2333/912 , G01N2333/98 , G01N2800/50 , G01N2800/52
摘要： The present disclosure provides for methods of treating a neurodegenerative condition, as well as methods for assessing the risk of developing a neurodegenerative condition, and assessing treatment efficacy in subjects who are carriers of the ApoE4 allele. Also disclosed is a method for diagnosing a neurodegenerative disorder.

8. 发明授权

US09119825B2 PKC-activating compounds for the treatment of neurodegenerative diseases 有权
标题翻译：用于治疗神经变性疾病的PKC活化化合物
公开(公告)号：US09119825B2
公开(公告)日：2015-09-01
申请号：US13401459
申请日：2012-02-21
申请人： Thomas J. Nelson , Daniel L. Alkon
发明人： Thomas J. Nelson , Daniel L. Alkon
IPC分类号： A61K31/045 , A61K31/201 , A61K31/335 , A61K31/231 , A61K31/23
CPC分类号： C07D303/42 , A61K31/045 , A61K31/201 , A61K31/23 , A61K31/231 , A61K31/335 , C07C31/13 , C07C31/1333 , C07C53/134 , C07C69/608 , C07D303/40 , C12N9/12 , C12Y207/11013
摘要： The present invention relates to methods of activate an isoform of protein kinase C (PKC) for the treatment of neurological diseases including Alzheimer's disease and stroke using cyclopropanated or epoxidized derivatives of mono- and polyunsaturated fatty acids. The present invention also relates to methods of reducing neurodegeneration using cyclopropanated or epoxidized derivatives of mono- and polyunsaturated fatty acids.
摘要翻译：本发明涉及使用单和多不饱和脂肪酸的环丙烷化或环氧化衍生物来激活蛋白激酶C（PKC）的同种型用于治疗包括阿尔茨海默氏病和中风的神经疾病的方法。本发明还涉及使用单和多不饱和脂肪酸的环丙烷化或环氧化衍生物减少神经变性的方法。

9. 发明申请

US20090029355A1 Abnormalities of Phosphatase 2A (PP2A) for Diagnosis and Treatment of Alzheimer's Disease 审中-公开
标题翻译：磷酸酶2A（PP2A）用于阿尔茨海默病诊断和治疗的异常
公开(公告)号：US20090029355A1
公开(公告)日：2009-01-29
申请号：US11660868
申请日：2004-11-15
申请人： Wei-Qin Zhao , Daniel L. Alkon
发明人： Wei-Qin Zhao , Daniel L. Alkon
IPC分类号： C12Q1/68 , C12Q1/42 , G01N33/53 , C07K16/00
CPC分类号： C12Q1/6883 , C12Q2600/136 , C12Q2600/158 , G01N33/6896
摘要： This invention relates to methods of diagnosing Alzheimer's disease and methods of screening for compounds for the treatment or prevention of Alzheimer's disease. The methods are based upon newly discovered differences in protein phosphatase 2A (PP2A) function and related molecular events in Alzheimer's disease cells compared to control cells. In one embodiment, differences in basal PP2A gene expression in Alzheimer's cells are compared to controls. In another embodiment differences in PP2A protein and enzyme activity are compared in test and control cells. In another embodiment differences in response to substances that inhibit PP2A function are compared. Still another embodiment detects differences in the subcellular distribution of phosphorylated Erk1/2, a substrate of PP2A, in normal and Alzheimer's disease cells. The detection of Alzheimer's disease-specific differences in PP2A function and related events in peripheral tissues provides the basis for highly practical and efficient tests and diagnostic test kits for the early diagnosis of Alzheimer's disease, as well as providing a biochemical basis for identifying therapeutic targets for drug development.
摘要翻译：本发明涉及诊断阿尔茨海默病的方法和筛选用于治疗或预防阿尔茨海默病的化合物的方法。该方法基于新发现的蛋白磷酸酶2A（PP2A）功能和阿尔茨海默病细胞相关分子事件与对照细胞相比的差异。在一个实施方案中，将阿尔茨海默氏病细胞中基础PP2A基因表达的差异与对照进行比较。在另一个实施方案中，在测试和对照细胞中比较了PP2A蛋白质和酶活性的差异。在另一个实施方案中，比较了抑制PP2A功能的物质的反应差异。另一个实施方案检测正常和阿尔茨海默氏病细胞中磷酸化Erk1 / 2（PP2A底物）的亚细胞分布的差异。检测外周组织中PP2A功能和相关事件中的阿尔茨海默病特异性差异为高龄实用和有效的测试和诊断试剂盒提供了基础，用于早期诊断阿尔茨海默氏病，并为确定治疗靶点提供了生物化学依据药物开发。

10. 发明授权

US5402522A Dynamically stable associative learning neural system 失效
标题翻译：动态稳定关联学习神经系统
公开(公告)号：US5402522A
公开(公告)日：1995-03-28
申请号：US80860
申请日：1993-06-22
申请人： Daniel L. Alkon , Thomas P. Vogl , Kim L. Blackwell
发明人： Daniel L. Alkon , Thomas P. Vogl , Kim L. Blackwell
IPC分类号： G06N3/04 , G06F15/18
CPC分类号： G06N3/04
摘要： A dynamically stable associative learning neural network system include a plurality of synapses (122,22-28), a non-linear function circuit (30) and an adaptive weight circuit (150) for adjusting the weight of each synapse based upon the present signal and the prior history of signals applied to the input of the particular synapse and the present signal and the prior history of signals applied to the input of a predetermined set of other synapses. An embodiment of a conditional-signal neuron circuit (100) receives input signals from conditional stimuli and an unconditional-signal neuron circuit (110) receives input signals from unconditional stimuli. A neural network (200) is formed by a set of conditional-signal and unconditional-signal neuron circuits connected by flow-through synapses to form separate paths between each input (215) and a corresponding output (245). In one embodiment, the neural network (200) is initialized by varying the weight of the input signals from conditional stimuli, until a dynamic equilibrium is reached.
摘要翻译：动态稳定的关联学习神经网络系统包括多个突触（122,22-28），非线性函数电路（30）和自适应加权电路（150），用于根据本信号调整每个突触的重量以及施加到特定突触的输入的信号的先前历史和当前信号以及施加到预定的其它突触组的输入的信号的先前历史。条件信号神经元电路（100）的实施例从条件刺激接收输入信号，无条件信号神经元电路（110）从无条件刺激接收输入信号。神经网络（200）由一组通过流通突触连接的条件信号和无条件信号神经元电路形成，以在每个输入（215）和相应的输出（245）之间形成分离的路径。在一个实施例中，通过改变来自条件刺激的输入信号的权重来初始化神经网络（200），直到达到动态平衡。

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