Abstract: A polytherapy of orally available compounds is disclosed that synergistically modulates and induces the expression of the cathelicidin gene (CAMP), which encodes the host defense peptide LL-37. By providing a number of different CAMP-inducing compounds together at the same time, stronger gene induction is achieved than with just one or two compounds, because the mechanism of induction broadens. Induction also may vary in different pas of the body depending on which compounds are used, and at what levels. We show for the first time that the polytherapy can induce cathelicidin expression in the brain, which may help to treat or prevent Alzheimer's Disease Systemic cathelicidin gene induction may help treat numerous other conditions including Type 2 Diabetes/Metabolic Syndrome, or chronic bacterial, viral, or fungal infections associated with increased cancer risk or neurodegeneration.

Abstract: Methods of treatment and pharmaceutical formulations configured to treat primary and secondary mitochondrial dysfunction are provided. The methods and treatments use an agonist of AMPK. The agonist activates AMPK to activate ATP-producing pathways and inhibiting ATP-consuming pathways, thus allowing for the alleviation of symptoms associated with mitochondrial dysfunctions.

Abstract: Adrenergic receptor modulating compounds and methods of using the same are provided. Also provided are methods of treating a subject for a disease or condition associated with an adrenergic receptor including administering a therapeutically effective amount of the subject compound. Aspects of the disclosure include a method of modulating an inflammatory pathway in a cell, such as the production of TNF-alpha in the cell. The method can include contacting a cell with ?1-selective adrenergic receptor modulating compound to selectively activate a cAMP pathway over a beta-arrestin pathway in the cell. Pharmaceutical compositions and kits which include the subject compounds are provided.

Abstract: Adrenergic receptor modulating compounds and methods of using the same are provided. Also provided are methods of treating a subject for a disease or condition associated with an adrenergic receptor including administering a therapeutically effective amount of the subject compound. Aspects of the disclosure include a method of modulating an inflammatory pathway in a cell, such as the production of TNF-alpha in the cell. The method can include contacting a cell with ?1-selective adrenergic receptor modulating compound to selectively activate a cAMP pathway over a beta-arrestin pathway in the cell. Pharmaceutical compositions and kits which include the subject compounds are provided.

Abstract: A polytherapy of orally available compounds is disclosed that synergistically modulates and induces the expression of the cathelicidin gene (CAMP), which encodes the host defense peptide LL-37. By providing a number of different CAMP-inducing compounds together at the same time, stronger gene induction is achieved than with just one or two compounds, because the mechanism of induction broadens. Induction also may vary in different parts of the body depending on which compounds are used, and at what levels. We show for the first time that the polytherapy can induce cathelicidin expression in the brain, which may help to treat or prevent Alzheimer's Disease. Systemic cathelicidin gene induction may help treat numerous other conditions including Type 2 Diabetes/Metabolic Syndrome, or chronic bacterial, viral, or fungal infections associated with increased cancer risk or neurodegeneration.

Abstract: A ?1-ADR agonist prodrug compound, which is hydrolysable in vivo to release a ?1-ADR agonist compound, and which prodrug compound contains a group which imparts greater lipophilicity and CNS bioavailability to the prodrug compound relative to the ?1-ADR agonist compound.

Abstract: A ?1-ADR agonist prodrug compound, which is hydrolysable in vivo to release a ?1-ADR agonist compound, and which prodrug compound contains a group which imparts greater lipophilicity and CNS bioavailability to the prodrug compound relative to the ?1-ADR agonist compound.

Abstract: A method for enhancing learning or memory of both in a mammal having impaired learning or memory of both from a neuro-degenerative disorder, which entails the step of administering at least one compound or a salt thereof which is a ?1-adrenergic receptor agonist, partial agonist or receptor ligand in an amount effective to improve the learning or memory or both of said mammal.

Abstract: A method for enhancing learning or memory of both in a mammal having impaired learning or emory of both from a neuro-degenerative disorder, which entails the step of administering at least one compound or a salt thereof which is a ?1-adrenergic receptor agonist, partial agonist or receptor ligand in an amount effective to improve the learning or memory or both of said mammal.

Abstract: The invention discloses methods and compositions useful for facilitating neuronal regeneration and functional recovery in neurodegenerative diseases. The methods and compositions utilize ligands for the sigma receptor, wherein the ligand is preferably AGY-94806, or salts, or solvates thereof. These molecules can be delivered alone or in combination with agents which treat or prevent neurodegenerative diseases such as those caused by multiple sclerosis. In other methods, the sigma receptor ligands are administered after MS to facilitate functional recovery. The administration of the sigma receptor ligands causes fasted functional recovery.

Abstract: The invention discloses methods and compositions useful for facilitating neuronal regeneration and functional recovery in neurodegenerative diseases. The methods and compositions utilize ligands for the sigma receptor, wherein the ligand is preferably AGY-94806, or salts, or solvates thereof. These molecules can be delivered alone or in combination with agents which treat or prevent neurodegenerative diseases such as those caused by multiple sclerosis. In other methods, the sigma receptor ligands are administered after MS to facilitate functional recovery. The administration of the sigma receptor ligands causes faster functional recovery.

Abstract: The invention discloses methods and compositions useful for facilitating neuronal regeneration and functional recovery in neurodegenerative diseases. The methods and compositions utilize ligands for the sigma receptor, wherein the ligand is preferably AGY-94806, or salts, or solvates thereof. These molecules can be delivered alone or in combination with agents which treat or prevent neurodegenerative diseases such as those caused by multiple sclerosis. In other methods, the sigma receptor ligands are administered after MS to facilitate functional recovery. The administration of the sigma receptor ligands causes faster functional recovery.

Abstract: Methods and compositions for the treatment of neurologic disorders involving neuronal death, including but not limited to focal or global ischemia of the brain and central nervous system. In vivo inhibition of 11 beta hydroxysteroid dehydrogenase 1 (HSD1) is shown to be neuroprotective in these conditions. HSD1 inhibitors are administered alone or in combination with additional agents for prophylaxis or therapy.

Abstract: The invention discloses methods and compositions useful for facilitating neuronal regeneration and functional recovery in neurodegenerative diseases. The methods and compositions utilize ligands for the sigma receptors. These molecules can be delivered alone or in combination with agents which treat or prevent neurodegenerative diseases such as those caused by ischemic stroke, diabetic peripheral neuropathy, cancer therapy induced neuropathy, multiple sclerosis, amyotrophic lateral sclerosis, traumatic brain injury, spinal cord injury, Huntington's disease or Parkinson's disease. In other methods, the sigma receptor ligands are administered after stroke to facilitate functional recovery. The administration of the sigma receptor ligands effects faster functional recovery.

Abstract: The present invention identifies a gene whose gene product provides a protective effect against neurological disorders or neuronal injuries. Further, the invention provides methods for diagnosing or assessing an individual's susceptibility to a neuronal injury such as stroke. Also provided are therapeutic methods for treating patients, and methods for prophylactically treating individuals susceptible to various neurological disorders or neuronal injuries. Additionally, the invention describes screening methods for identifying agents that can be administered to treat individuals that have suffered or are at risk to suffer such disorders or injuries.

Abstract: The present invention identifies the K11 gene, whose gene products can be modulated to provide a protective effect against stroke, especially ischemic stroke, epilepsy and neurodegenerative disorders and enhancement of memory function. Further, the invention provides methods for diagnosing or assessing an individual's susceptibility to a stroke. Also provided are therapeutic methods for treating a stroke patient or methods for prophylactically treating an individual susceptible to stroke. Additionally, the invention describes screening methods for identifying agents that can be administered to treat individuals that have suffered a stroke or that are at risk for stroke.

Abstract: The present invention identifies a gene whose gene product provides a protective effect against neurological disorders or neuronal injuries. Further, the invention provides methods for diagnosing or assessing an individual's susceptibility to a neuronal injury such as stroke. Also provided are therapeutic methods for treating patients, and methods for prophylactically treating individuals susceptible to various neurological disorders or neuronal injuries. Additionally, the invention describes screening methods for identifying agents that can be administered to treat individuals that have suffered or are at risk to suffer such disorders or injuries.