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    ALZHEIMER'S DISEASE-SPECIFIC ALTERATIONS OF PROTEIN KINASE C EPSILON (PKC-EPSILON) PROTEIN LEVELS
    2.
    发明申请
    ALZHEIMER'S DISEASE-SPECIFIC ALTERATIONS OF PROTEIN KINASE C EPSILON (PKC-EPSILON) PROTEIN LEVELS 审中-公开
    蛋白激酶C蛋白激酶（PKC-EPSILON）蛋白水平的ALZHEIMER疾病特异性改变

    公开(公告)号：WO2011102907A1

    公开(公告)日：2011-08-25

    申请号：PCT/US2011/000315

    申请日：2011-02-22

    申请人： BLANCHETTE ROCKEFELLER NEUROSCIENCES INSTITUTE ,  KHAN, Tapan, K. ,  ALKON, Daniel, L.

    发明人： KHAN, Tapan, K. ,  ALKON, Daniel, L.

    IPC分类号： G01N33/48 ,  G01N33/53

    CPC分类号： C12Q1/485 ,  C12Q1/68 ,  C12Q1/6883 ,  G01N33/573 ,  G01N33/6896 ,  G01N2333/912 ,  G01N2800/2821

    摘要： The present invention relates to methods of diagnosing Alzheimer's Disease in a human patient by detecting alterations in the ratio of PKC epsilon protein levels in a human patient compared with PKC epsilon levels in a control subject. The Alzheimer's disease- specific molecular biomarkers disclosed herein are useful for the diagnosis of Alzheimer's disease and for screening methods for the identification of compounds for treating or preventing Alzheimer's disease. The present invention also provides methods for elevating PKC epsilon protein levels comprising the steps of contacting one or more human cells with an amount of a PKC activator effective to elevate PKC epsilon levels compared to an uncontacted human cell.

    摘要翻译： 本发明涉及通过检测人类患者中PKCε蛋白水平与对照受试者中的PKCε水平相比的变化来诊断人类患者中的阿尔茨海默病的方法。 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病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。 本发明还提供了用于升高PKCε蛋白水平的方法，其包括以下步骤：使一个或多个人细胞与一定量的PKC激活剂相接触，以有效提高PKCε水平与未接触的人细胞相比。

    ALZHEIMER'S DISEASE-SPECIFIC ALTERATIONS OF THE ERK1/ERK2 PHOSPHORYLATION RATIO-ALZHEIMER'S DISEASE-SPECIFIC MOLECULAR BIOMARKERS (ADSMB)
    5.
    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
    ALZHEIMER的ERK1 / ERK2磷酸化比例阿尔茨海默病特异性分子生物标志物（ADSMB）的疾病特异性改变

    公开(公告)号：WO2009126232A1

    公开(公告)日：2009-10-15

    申请号：PCT/US2009/002120

    申请日：2009-04-03

    申请人： BLANCHETTE ROCKEFELLER NEUROSCIENCES INSTITUTE ,  KHAN, Tapan, Kumar ,  ALKON, Daniel, L.

    发明人： KHAN, Tapan, Kumar ,  ALKON, Daniel, L.

    IPC分类号： G01N33/68

    CPC分类号： G01N33/6896 ,  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。

    THERAPEUTIC EFFECTS OF BRYOSTATINS, BRYOLOGS, AND OTHER RELATED SUBSTANCES ON HEAD TRAUMA-INDUCED MEMORY IMPAIRMENT AND BRAIN INJURY
    6.
    发明申请
    THERAPEUTIC EFFECTS OF BRYOSTATINS, BRYOLOGS, AND OTHER RELATED SUBSTANCES ON HEAD TRAUMA-INDUCED MEMORY IMPAIRMENT AND BRAIN INJURY 审中-公开
    BRYOSTATINS，BRYOSS和其他相关物质对头部TRAUMA诱导的记忆损伤和脑损伤的治疗效果

    公开(公告)号：WO2008100449A2

    公开(公告)日：2008-08-21

    申请号：PCT/US2008001755

    申请日：2008-02-11

    申请人： BRNI NEUROSCIENCES INST ,  ZOHAR OFER ,  ALKON DANIEL L

    发明人： ZOHAR OFER ,  ALKON DANIEL L

    IPC分类号： A61K38/18 ,  A61K38/22 ,  A61K38/31

    CPC分类号： A61K38/1825 ,  A61K31/00 ,  A61K31/05 ,  A61K31/335 ,  A61K31/35 ,  A61K31/365 ,  A61K31/395 ,  A61K31/4015 ,  A61K38/00

    摘要： The invention provides for the use of protein kinase activators or boosters of nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) or other neurotrophic factors to treat head trauma. Specifically, the present invention provides methods of treating head trauma comprising the steps of identifying a subject having suffered a head trauma and administering to said subject an amount of a pharmaceutical composition comprising a protein kinase C (PKC) activator or 4-methylcatechol acetic acid (MCBA) and a pharmaceutically acceptable carrier effective to treat at least one symptom of head trauma.

    摘要翻译： 本发明提供使用蛋白激酶激活剂或神经生长因子（NGF）的促进剂，脑源性神经营养因子（BDNF）或其他神经营养因子来治疗头部创伤。 具体地，本发明提供了治疗头部创伤的方法，其包括以下步骤：鉴定遭受头部创伤的受试者，并向所述受试者施用一定量的包含蛋白激酶C（PKC）激活剂或4-甲基儿茶酚乙酸的药物组合物 MCBA）和有效治疗头部创伤的至少一种症状的药学上可接受的载体。

    CONTROLLING ATTENTION AND MEMORY BY ALTERING NEURONAL CARBONIC ANHYDRASE ACTIVITY
    9.
    发明申请
    CONTROLLING ATTENTION AND MEMORY BY ALTERING NEURONAL CARBONIC ANHYDRASE ACTIVITY 审中-公开
    通过改变神经元碳氢化合物活性来控制注意和记忆

    公开(公告)号：WO0193744A3

    公开(公告)日：2003-02-06

    申请号：PCT/US0118329

    申请日：2001-06-07

    申请人： US GOV HEALTH & HUMAN SERV ,  SUN MIAO-KUN ,  ALKON DANIEL L ,  ZHAO WEI-QIN

    发明人： SUN MIAO-KUN ,  ALKON DANIEL L ,  ZHAO WEI-QIN

    IPC分类号： A61K31/00 ,  A61K31/433 ,  A61K38/43 ,  C07H21/04 ,  C12N15/11 ,  C12N15/85 ,  C12N15/86 ,  G01N33/53

    CPC分类号： A61K31/00 ,  A61K31/433

    摘要： The invention provides a method for modulating attentive cognition comprising administering a compound that alters intraneuronal carbonic anhydrase activity thereby affecting establishment of a theta rhythm. The metabolic pathway of the compound preferably involves bicarbonate-mediated GABAergic depolarization. The term "attentive cognition" is meant to encompass memory formation, learning, spatial memory, and attention. The modulating may be stimulating, or the compound may have the multiple effects of inhibiting intraneuronal carbonic anhydrase activity, establishment of a theta rhythm, and memory acquisition. The invention further provides a method of modulating memory and attention comprising switching theta rhythm on and off, the switching comprising potentiating or inhibiting intraneuronal carbonic anhydrase activity.

    摘要翻译： 本发明提供了一种调节注意认知的方法，包括施用改变内源性碳酸酐酶活性从而影响θ节律的建立的化合物。 该化合物的代谢途径优选包括碳酸氢盐介导的GABA能去极化。 术语“细心认知”意在包括记忆形成，学习，空间记忆和关注。 调节可能是刺激的，或者化合物可能具有抑制内源性碳酸酐酶活性，建立θ节律和记忆获取的多种作用。 本发明还提供了一种调节记忆和注意力的方法，包括打开和关闭θ节律，切换包括增强或抑制内源性碳酸酐酶活性。

    PROTEIN KINASE C ACTIVATORS AND ANTICOAGULANT FOR THE TREATMENT OF STROKE
    10.
    发明申请
    PROTEIN KINASE C ACTIVATORS AND ANTICOAGULANT FOR THE TREATMENT OF STROKE 审中-公开
    蛋白激酶C激活剂和抗凝剂治疗痤疮

    公开(公告)号：WO2012006516A3

    公开(公告)日：2012-03-15

    申请号：PCT/US2011043346

    申请日：2011-07-08

    申请人： ALKON DANIEL L

    发明人： ALKON DANIEL L

    IPC分类号： A61K31/20 ,  A61K31/366 ,  A61K38/49 ,  A61P9/10

    CPC分类号： A61K38/49 ,  A61K9/0019 ,  A61K31/20 ,  A61K31/366 ,  C12Y304/21068 ,  A61K2300/00

    摘要： The present disclosure provides a method for treating stroke by administering an anticoagulant, e.g., recombinant tissue plasminogen activator (rTPA), and a protein kinase C (PKC) activator, wherein the PKC activator may be administered before, after, or at the same time as the rTPA. The methods disclosed herein may limit the size of infarction and/or reduce mortality, the disruption of the blood-brain barrier, and/or the hemorrhagic damage due to ischemic stroke compared with rTPA administration alone; and may also extend the therapeutic time window for administering rTPA after a stroke. Also disclosed are compositions and kits comprising rTPA and a PKC activator for treating stroke.

    摘要翻译： 本公开提供了一种通过施用抗凝血剂（例如重组组织纤溶酶原激活物（rTPA））和蛋白激酶C（PKC）激活剂来治疗中风的方法，其中PKC激活剂可以在之前，之后或同时施用 作为rTPA。 与单独的rTPA给药相比，本文公开的方法可以限制梗塞的大小和/或降低死亡率，血脑屏障的破坏和/或由于缺血性卒中引起的出血性损伤; 并且还可以延长在卒中后施用rTPA的治疗时间窗口。 还公开了包含用于治疗中风的rTPA和PKC激活剂的组合物和试剂盒。