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公开(公告)号：US07977377B2
公开(公告)日：2011-07-12
申请号：US11802724
申请日：2007-05-24
申请人： Miao-Kun Sun , Daniel L. Alkon , Thomas J. Nelson
发明人： Miao-Kun Sun , Daniel L. Alkon , Thomas J. Nelson
IPC分类号： A61K31/335 , A61K31/351 , A61P25/24
CPC分类号： A61K38/1825 , A61K31/045 , A61K31/05 , A61K31/192 , A61K31/196 , A61K31/365 , A61K31/366 , A61K31/4164 , A61K31/4172
摘要： The invention provides for the use of carbonic anhydrase activators; protein kinase C activators and FGF-18 to treat depressive disorders. The invention also relates to improved animal models and methods for screening and identifying compounds the treatment of depressive disorders.
摘要翻译： 本发明提供了使用碳酸酐酶活化剂; 蛋白激酶C激活剂和FGF-18治疗抑郁障碍。 本发明还涉及用于筛选和鉴定化合物治疗抑郁症的改进的动物模型和方法。
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公开(公告)号：US20110136144A1
公开(公告)日：2011-06-09
申请号：US12896862
申请日：2010-10-02
IPC分类号： G01N33/567 , C12Q1/02 , C40B40/02
CPC分类号： G01N33/5091 , G01N33/6896 , G01N2800/2821
摘要： Methods of diagnosing Alzheimer's disease are provided. At least five methods of diagnostic measurements are presented: Method 1: Integrated score; Method 2: Average aggregate area per number of aggregates; Method 3: Cell migration analysis; Method 4; Fractal analysis; Method 5: Lacunarity Analysis. In certain embodiments, a sample of a subject's skin provides a network of fibroblasts that is imaged and a fractal dimension of the image is calculated. The fractal dimension can be compared to an aged-matched control (non-Alzheimer's) database to determine if the subject has Alzheimer's disease. The network of fibroblasts may be cultured in a matrix, for example in a protein mixture.
摘要翻译： 提供了诊断阿尔茨海默病的方法。 提出了至少五种诊断测量方法：方法1：综合评分; 方法2：每个聚集体的平均聚集面积; 方法3：细胞迁移分析; 方法4; 分形分析; 方法5：Lacunarity分析。 在某些实施方案中，受试者皮肤的样品提供成像的成纤维细胞的网络，并且计算图像的分形维数。 可以将分形维数与老年匹配对照（非阿尔茨海默病）数据库进行比较，以确定受试者是否患有阿尔茨海默氏病。 成纤维细胞的网络可以在基质中培养，例如在蛋白质混合物中。
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53.发明申请PROTEIN SYNTHESIS REQUIRED FOR LONG-TERM MEMORY IS INDUCED BY PKC ACTIVATION ON DAYS PRECEDING ASSOCIATIVE LEARNING 审中-公开需要长时间记忆的蛋白质合成是由PKC激活导致的相关学习日公开(公告)号：US20100303792A1
公开(公告)日：2010-12-02
申请号：US12851222
申请日：2010-08-05
申请人： Daniel L. Alkon
发明人： Daniel L. Alkon
CPC分类号： A61K31/366 , A61K31/365 , A61K31/40 , A61K31/4015 , A61K31/407 , A61K31/437
摘要： The present invention provides methods of contacting a protein kinase C (PKC) activator with a PKC activator in a manner sufficient to stimulate the synthesis of proteins sufficient to consolidate long-term memory. The present invention also provides methods of contacting a protein kinase C (PKC) activator with a PKC activator in a manner sufficient to downregulate PKC.
摘要翻译： 本发明提供使蛋白激酶C（PKC）激活剂与PKC激活剂以足以刺激足以巩固长期记忆的蛋白质合成的方式接触的方法。 本发明还提供了以足以下调PKC的方式使蛋白激酶C（PKC）活化剂与PKC激活剂接触的方法。
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54.发明申请PKC activation as a means for enhancing sAPPALPHA secretion and improving cognition using bryostatin type compounds 审中-公开PKC活化作为增强sAPPALPHA分泌和改善使用苔藓抑素型化合物的认知的手段公开(公告)号：US20090030055A1
公开(公告)日：2009-01-29
申请号：US11802726
申请日：2007-05-24
申请人： Thomas Nelson , Daniel L. Alkon
发明人： Thomas Nelson , Daniel L. Alkon
IPC分类号： A61K31/4196 , A61K31/357 , A61K31/407 , A61K31/11 , A61K31/216 , A61K31/18 , A61K31/20 , C12N5/02
CPC分类号： A61K31/11 , A61K31/18 , A61K31/20 , A61K31/216 , A61K31/357 , A61K31/407 , A61K31/4196 , A61K2300/00
摘要： The present invention relates to compositions and methods to modulate α-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。
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55.发明申请Alzheimer's disease-specific alterations of the ERK1/ERK2 Phosphorylation ratio-Alzheimer's disease-specific molecular biomarkers (ADSMB) 审中-公开ERK1 / ERK2磷酸化比例的阿尔茨海默病特异性改变 - 阿尔茨海默病特异性分子生物标志物（ADSMB）公开(公告)号：US20080221042A1
公开(公告)日：2008-09-11
申请号：US12078857
申请日：2008-04-07
申请人： Tapan Kumar Khan , Daniel L. Alkon
发明人： Tapan Kumar Khan , Daniel L. Alkon
CPC分类号： G01N33/6896 , A61K38/043 , A61K38/095 , A61K38/105 , A61K38/2207 , A61K38/4833 , G01N2800/2821 , G01N2800/52
摘要： The present invention relates to methods of diagnosing Alzheimer's Disease as well as to methods of confirming the presence or absence of Alzheimer's Disease in a subject. The present invention is also directed to methods of identifying a lead compound useful for the treatment of Alzheimer's Disease by contacting non-Alzheimer's cells with an amyloid beta peptide, stimulating the cells with a protein kinase C activator, contacting the cells with a test compound, and determining the value of an Alzheimer's Disease-specific molecular biomarker. The present invention is also directed to methods of diagnosing Alzheimer's Disease in a subject by detecting alterations in the ratio of specific phosphorylated MAP kinase proteins in cells after stimulation with a protein kinase C activator. The Alzheimer's Disease-specific molecular biomarkers disclosed herein are useful for the diagnosis of Alzheimer's Disease, monitoring the progression of Alzheimer's Disease in a subject and in screening methods for the identification of compounds for treating or preventing Alzheimer's Disease. The invention is also directed to kits containing reagents for the detection and diagnosis of the presence or absence of Alzheimer's Disease using the Alzheimer's Disease-specific molecular biomarkers disclosed herein.
摘要翻译： 本发明涉及诊断阿尔茨海默病的方法以及确认受试者中是否存在阿尔茨海默氏病的方法。 本发明还涉及通过使非阿尔茨海默病细胞与淀粉状蛋白β肽接触，用蛋白激酶C激活剂刺激细胞，使细胞与测试化合物接触来鉴定用于治疗阿尔茨海默病的铅化合物的方法， 并确定阿尔茨海默氏病特异性分子生物标志物的价值。 本发明还涉及通过检测用蛋白激酶C激活剂刺激后细胞中特异性磷酸化MAP激酶蛋白的比例变化来诊断受试者中的阿尔茨海默氏病的方法。 本文公开的阿尔茨海默病特异性分子生物标志物可用于诊断阿尔茨海默氏病，监测受试者中阿尔茨海默氏病的进展和用于鉴定用于治疗或预防阿尔茨海默氏病的化合物的筛选方法。 本发明还涉及包含用于使用本文公开的阿尔茨海默病特异性分子生物标志物来检测和诊断阿尔茨海默氏病或不存在的试剂的试剂盒。
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公开(公告)号：US06825229B2
公开(公告)日：2004-11-30
申请号：US10167491
申请日：2002-06-13
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。
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公开(公告)号：US06821979B2
公开(公告)日：2004-11-23
申请号：US10172005
申请日：2002-06-17
申请人： Daniel L. Alkon , Miao-Kun Sun
发明人： Daniel L. Alkon , Miao-Kun Sun
IPC分类号： A61K3152
CPC分类号： A61K31/417 , A61K31/135 , A61K31/198 , A61K31/4172 , A61K31/52 , A61K2300/00
摘要： The present invention relates to the combination of a methylxanthine and a carbonic anhydrase activator to provide synergistic effects. The invention further relates to the improved/enhanced cognitive ability of individuals, particularly those suffering from various disorders, such as Alzheimer's Disease, stroke, hypoxia, general dementia, ADHD, mental retardation, and “sun down” syndrome.
摘要翻译： 本发明涉及甲基黄嘌呤和碳酸酐酶活化剂的组合以提供协同效应。 本发明还涉及个体，特别是患有诸如阿尔茨海默氏病，中风，缺氧，一般性痴呆，ADHD，智力低下和“下垂”综合症等各种疾病的个体的改善/增强的认知能力。
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公开(公告)号：US5976816A
公开(公告)日：1999-11-02
申请号：US312202
申请日：1994-09-26
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。
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公开(公告)号：US5870493A
公开(公告)日：1999-02-09
申请号：US819142
申请日：1997-03-17
CPC分类号： G06K9/4628
摘要： An image recognition and classification system includes a preprocessor in which a "top-down" method is used to extract features from an image; an associative learning neural network system, which groups the features into patterns and classifies the patterns: and a feedback mechanism which improves system performance by tuning preprocessor scale, feature detection, and feature selection.
摘要翻译： 图像识别和分类系统包括其中使用“自顶向下”方法从图像中提取特征的预处理器; 一种联想学习神经网络系统，将特征组合成模式并对模式进行分类：通过调整预处理器规模，特征检测和特征选择来提高系统性能的反馈机制。
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公开(公告)号：US5446829A
公开(公告)日：1995-08-29
申请号：US82003
申请日：1993-06-24
申请人： Lipo Wang , Daniel L. Alkon
发明人： Lipo Wang , Daniel L. Alkon
CPC分类号： G06K9/72 , G06N3/0454 , G06N3/049
摘要： A computer-based artificial network is presented that is capable of learning, recognizing, and generating temporal-spatial sequences. The network system includes time-delays and artificial neural subnetworks. The system generally includes three parts: (1) comparator units, (2) a parallel array of subnetworks and (3) delayed feedback lines from the output of the system to the neural subnetwork layer.
摘要翻译： 提出了一种能够学习，识别和生成时空序列的基于计算机的人造网络。 网络系统包括时间延迟和人工神经子网。 该系统通常包括三个部分：（1）比较器单元，（2）子网络的平行阵列和（3）从系统输出到神经子网层的延迟反馈线。
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