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11. 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.

12. 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。

13. 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。

14. 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。

15. 发明授权

US09974832B2 Therapeutic effects of bryostatins, bryologs, and other related substances on head trauma-induced memory impairment and brain injury 有权
公开(公告)号：US09974832B2
公开(公告)日：2018-05-22
申请号：US12068742
申请日：2008-02-11
申请人： Ofer Zohar , Daniel L. Alkon
发明人： Ofer Zohar , Daniel L. Alkon
IPC分类号： A61K31/366 , A61K31/192 , A61K38/18 , A61K31/00 , A61K31/05 , A61K31/335 , A61K31/35 , A61K31/365 , A61K31/395 , A61K31/4015 , A61K38/00
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.

16. 发明授权

US09597312B2 Treatment of cognitive disorders associated with abnormal dendritic spines using PKC activators 有权
公开(公告)号：US09597312B2
公开(公告)日：2017-03-21
申请号：US13817040
申请日：2011-08-19
申请人： Miao-kun Sun , Daniel L. Alkon
发明人： Miao-kun Sun , Daniel L. Alkon
IPC分类号： A61K31/365
CPC分类号： A61K31/365
摘要： The present disclosure provides methods of treating a cognitive disorder associated with abnormal dendritic spines, such as Fragile X Syndrome, Fragile X Associated Tremor/Ataxia Syndrome, autism, or mental retardation, using PKC activators.

17. 发明申请

US20120149768A1 PKC-ACTIVATING COMPOUNDS FOR THE TREATMENT OF NEURODEGENERATIVE DISEASES 有权
标题翻译：用于治疗神经损伤性疾病的PKC-活化化合物
公开(公告)号：US20120149768A1
公开(公告)日：2012-06-14
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： A61K31/336 , A61K31/20 , C07C53/134 , C07C69/608 , C07D303/38 , A61P25/24 , C07C31/13 , A61K31/045 , A61K31/215 , A61K31/19 , A61P25/28 , C12N9/12 , C07C53/132
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）的同种型以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。

18. 发明申请

US20110245307A1 Methods for Alzheimer's Disease Treatment and Cognitive Enhancement 审中-公开
标题翻译：阿尔茨海默病治疗和认知增强方法
公开(公告)号：US20110245307A1
公开(公告)日：2011-10-06
申请号：US13042892
申请日：2011-03-08
申请人： Daniel L. Alkon
发明人： Daniel L. Alkon
IPC分类号： A61K31/4196 , A61K31/18 , A61K31/235 , A61K31/11 , A61K31/357 , A61K31/407 , A61K31/351 , A61P25/28 , C12N5/02 , A61P25/16
CPC分类号： A61K31/335 , A61K31/00 , A61K31/355 , A61K31/365 , A61K31/366 , A61K31/40 , A61K2300/00
摘要： The present invention relates to compositions comprising a combination of PKC activators and PKC inhibitors and methods to modulate α-secretase activity; improve or enhance cognitive ability; and/or reduce neurodegeneration in individuals suffering from diseases that impair cognitive ability, particularly Alzheimer's Disease. The invention also relates to methods for improving or enhancing cognitive ability. The present invention also provides methods for increasing the generation of non-amyloidogenic soluble APP (sAPP) comprising the activation of protein kinase C (PKC) in the brain and inhibiting PKC in peripheral tissues. Macrocyclic lactones (i.e. bryostatin class and neristatin class) are preferred PKC activators and Vitamin E is a preferred PKC inhibitor for use in the inventive composition.
摘要翻译：本发明涉及包含PKC激活剂和PKC抑制剂的组合的组合物和调节α-分泌酶活性的方法; 提高或提高认知能力; 和/或减少患有认知能力的疾病，特别是阿尔茨海默病的个体的神经变性。本发明还涉及用于改善或增强认知能力的方法。本发明还提供了增加包含脑中蛋白激酶C（PKC）活化并抑制外周组织中PKC的非淀粉样蛋白可溶性APP（sAPP）的产生的方法。大环内酯（即苔藓抑制素类和神经抑制素类）是优选的PKC活化剂，维生素E是用于本发明组合物的优选PKC抑制剂。

19. 发明授权

US07803400B2 Artificial low-density lipoprotein carriers for transport of substances across the blood-brain barrier 有权
公开(公告)号：US07803400B2
公开(公告)日：2010-09-28
申请号：US11802727
申请日：2007-05-24
申请人： Thomas J. Nelson , Daniel L. Alkon , Alessandro Quattrone
发明人： Thomas J. Nelson , Daniel L. Alkon , Alessandro Quattrone
IPC分类号： A61K9/14 , A61K31/195 , A61K38/02 , A61P43/00
CPC分类号： A61K9/127 , A61K9/1275 , A61K31/195 , A61K31/56 , A61K31/70 , A61K31/704 , A61K31/7088 , A61K38/1709
摘要： This invention relates to a highly efficient artificial low-density lipoprotein (LDL) carrier system for the targeted delivery therapeutic agents across the blood-brain barrier (BBB). In particular, this invention relates to artificial LDL particles comprised of three lipid elements: phosphatidyl choline, fatty-acyl-cholesterol esters, and at least one apolipoprotein. The present invention further relates to compositions, methods and kits comprising artificial LDL particles for targeting drugs to and across the BBB for the prevention and treatment of brain diseases.

20. 发明授权

US06552053B2 Controlling attention and memory by altering neuronal carbonic anhydrase activity 失效
公开(公告)号：US06552053B2
公开(公告)日：2003-04-22
申请号：US09875283
申请日：2001-06-07
申请人： Miao-Kun Sun , Daniel L. Alkon , Wei-Qin Zhao
发明人： Miao-Kun Sun , Daniel L. Alkon , Wei-Qin Zhao
IPC分类号： A61K3141
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.

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