Abstract: Dosing regimens and methods are disclosed for upregulating on protein kinase C (PKC) while reducing subsequent downregulation, comprising administering a PKC activator once a week for three consecutive weeks followed by cessation of administration or dosing for three consecutive weeks. Also described are methods for improving or enhancing cognitive ability, preventing or treating cognitive impairment, preventing or treating a neurodegenerative disease or condition, and/or preventing or treating a disease or condition associated with neuronal or synaptic loss according to the disclosed regimens.

Abstract: This invention provides methods for diagnosing Alzheimer's disease in a symptomatic human subject, and for determining whether a human subject is predisposed to becoming afflicted with Alzheimer's disease. These methods employ the steps of (a) culturing a subject's lymphocytes with a suitable basement membrane matrix to permit the lymphocytes to aggregate; (b) measuring the resulting lymphocyte aggregation; and (c) based on such measurement, either diagnosing Alzheimer's disease or determining a predisposition to it, as appropriate.

Abstract: This invention provides methods for diagnosing Alzheimer's disease in a symptomatic human subject, and for determining whether a human subject is predisposed to becoming afflicted with Alzheimer's disease. These methods involve the steps of (a) culturing lymphocytes from the subject under suitable conditions; (b) measuring the amount of PKC? in the cultured lymphocytes; and (c) comparing the measurement of step (b) with a suitable control.

Abstract: The PKC activator bryostatin-1 and its analogs increase the survival of dermal fibroblast cells. Bryostatin and picolog, a synthetic analog, are used as candidate therapeutic agents for improving the appearance of aging skin, reducing scar tissue formation, and improving the acceptance of a clinical skin grafts.

Abstract: 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.

Abstract: 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 to treat depressive disorders.

Abstract: 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.

Abstract: The present disclosure describes novel PKC-? activators chosen from halogenated esters of unsaturated fatty acids derivatives thereof, including halogenated esters of both polyunsaturated and monunsaturated fatty acids and derivatives thereof. The disclosure further relates to compositions, kits, and methods for treatment using the halogenated esters.

Abstract: The present disclosure is directed to compositions comprising bryostatin-1, and methods comprising administering a composition comprising bryostatin-1, to treat Niemann-Pick Type C in a subject in need thereof.

Abstract: The present disclosure provides a method for treating stroke by administering to a subject an anticoagulant, e.g., recombinant tissue plasminogen activator (rTPA), and a protein kinase C (PKC) activator followed by administration of at least one PKC activator for a duration of treatment. 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 kits comprising rTPA and a PKC activator for treating stroke.

Abstract: 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.

Abstract: The present disclosure is directed to compositions comprising bryostatin-1, and methods comprising administering a composition comprising bryostatin-1, to treat Niemann-Pick Type C in a subject in need thereof.

Abstract: The present invention provides methods of slowing or reversing the loss of memory and learning comprising the steps of contacting an effective amount of a PKC activator with a protein kinase C (PKC) in a subject identified with memory loss slowing or reversing memory loss. The present invention provides methods of stimulating cellular growth, neuronal growth, dendritic growth, dendritic spine formation, dendritic spine density, and the translocation of ELAV to proximal dendrites, and synaptic remodeling. The present invention also 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.

Abstract: 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-Alzheimers 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.

Abstract: The present disclosure is directed to compositions comprising bryostatin-1, and methods comprising administering a composition comprising bryostatin-1, to treat Niemann-Pick Type C in a subject in need thereof.

Abstract: 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.

Abstract: The present disclosure describes diagnostics for Alzheimer's disease based on the discovery of an increased aggregation rate with increasing cell density in cells from Alzheimer-disease patients versus controls. The aggregation rate was cross-validated with two more mature assays: AD-Index and Morphology diagnostic assays. Also disclosed is a simple-majority rule for diagnosing AD using at least three diagnostic assays, such as the Aggregation Rate, AD-Index, and Morphology assays.

Abstract: The present invention relates to compositions and methods to modulate ?-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).

Abstract: The present invention relates to compositions and methods to modulate ?-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).

Abstract: The present disclosure describes novel PKC-? activators chosen from halogenated esters of unsaturated fatty acids derivatives thereof, including halogenated esters of both polyunsaturated and monunsaturated fatty acids and derivatives thereof. The disclosure further relates to compositions, kits, and methods for treatment using the halogenated esters.