Abstract: The present invention provides a method of treating a disease or disorder caused by and/or associated with CSF1R dysfunction in a human patient, the method comprising administering to the patient in need thereof an effective amount of a compound that increases the activity of triggering receptor expressed on myeloid cells 2 (TREM2). In some embodiments, compound that increases the activity of TREM2 is an agonist of TREM2. In some embodiments, the agonist of TREM2 is a small molecule agonist of TREM2 or an antibody agonist of TREM2.

Abstract: Methods and pharmaceutical compositions comprising a low dose of a farnesyl transferase inhibitor useful in the treatment of proteinopathies are provided. These low doses are below the doses used in oncological treatments for which these compounds were initially designed. The treatment includes administering to a subject in need thereof a therapeutically effective amount of a farnesyl transferase inhibitor, wherein the amount is effective to inhibit the farnesylation of a non-Ras FTase substrate involved in the autophagy pathway without substantially affecting the farnesylation of Ras or other oncology related substrates. Treatments in accordance with the present invention may also include an acetylcholinesterase inhibitor, an activator of neurotrophic receptors, an NMDA anatagonist, an amyloid deposit inhibitor, an antipsychotic agent, an antidepressant, an anxiolytic, or an antioxidant.

Abstract: Methods and pharmaceutical compositions comprising a low dose of a farnesyl transferase inhibitor useful in the treatment of proteinopathies and mitochondrial disorders are provided. These low doses are below the doses used in oncological treatments for which these compounds were initially designed. The treatment includes administering to a subject an amount of a farnesyl transferase inhibitor, wherein the amount administered is sufficient to stimulate mitophagy in said subject. Treatments in accordance with the present invention may also include an acetylcholinesterase inhibitor, an activator of neurotrophic receptors, an NMDA anatagonist, an amyloid deposit inhibitor, an antipsychotic agent, an antidepressant, an anxiolytic, or an antioxidant.

Abstract: Methods and pharmaceutical compositions comprising a low dose of a farnesyl transferase inhibitor useful in the treatment of proteinopathies are provided. These low doses are below the doses used in oncological treatments for which these compounds were initially designed. The treatment includes administering to a subject an amount of a farnesyl transferase inhibitor, wherein the amount administered is sufficient to cause an improvement in mitochondrial health in said subject. Treatments in accordance with the present invention may also include an acetylcholinesterase inhibitor, an activator of neurotrophic receptors, an NMDA anatagonist, an amyloid deposit inhibitor, an antipsychotic agent, an antidepressant, an anxiolytic, or an antioxidant.

Abstract: Methods and pharmaceutical compositions comprising a low dose of a farnesyl transferase inhibitor useful in the treatment of proteinopathies are provided. These low doses are below the doses used in oncological treatments for which these compounds were initially designed. The treatment includes administering to a subject in need thereof a therapeutically effective amount of a farnesyl transferase inhibitor, wherein the amount is effective to inhibit the farnesylation of a non-Ras FTase substrate involved in the autophagy pathway without substantially affecting the farnesylation of Ras or other oncology related substrates. Treatments in accordance with the present invention may also include an acetylcholinesterase inhibitor, an activator of neurotrophic receptors, an NMDA antagonist, an amyloid deposit inhibitor, an antipsychotic agent, an antidepressant, an anxiolytic, or an antioxidant.

Abstract: The present invention is drawn to methods of characterization of the properties and functions of SV2 proteins. The invention further includes methods of identifying compounds or agents which modulate the activity of SV2 proteins. Included in these methods is the identification of compounds or agents which modulate the binding of levetiracetam to SV2 proteins, including SV2A. Additionally, the present invention provides biotinylated ligands as a tool to screen chemical libraries and characterize the SV2 proteins. Further, the present invention provides a method of solubilizing and purifying functionally active membrane associated proteins, such as SV2.

Abstract: The present invention is drawn to methods of characterization of the properties and functions of SV2 proteins. The invention further includes methods of identifying compounds or agents which modulate the activity of SV2 proteins. Included in these methods is the identification of compounds or agents which modulate the binding of levetiracetam to SV2 proteins, including SV2A. Additionally, the present invention provides biotinylated ligands as a tool to screen chemical libraries and characterize the SV2 proteins. Further, the present invention provides a method of solubilizing and purifying functionally active membrane associated proteins, such as SV2.

Abstract: The present invention is drawn to methods of characterization of the properties and functions of SV2 proteins. The invention further includes methods of identifying compounds or agents which modulate the activity of SV2 proteins. Included in these methods is the identification of compounds or agents which modulate the binding of levetiracetam SV2 proteins, including SV2A.

Abstract: The present invention is drawn to methods of characterization of the properties and functions of SV2 proteins. The invention further includes methods of identifying compounds or agents which modulate the activity of SV2 proteins. Included in these methods is the identification of compounds or agents which modulate the binding of levetiracetam to SV2 proteins, including SV2A. Additionally, the present invention provides biotinylated ligands as a tool to screen chemical libraries and characterize the SV2 proteins. Further, the present invention provides a method of solubilizing and purifying functionally active membrane associated proteins, such as SV2.

Abstract: The present invention is drawn to methods of characterization of the properties and functions of SV2 proteins. The invention further includes methods of identifying compounds or agents which modulate the activity of SV2 proteins. Included in these methods is the identification of compounds or agents which modulate the binding of levetiracetam SV2 proteins, including SV2A.

Abstract: An in vitro assay method permits the identification of a test substance which inhibits the mutual association of two molecules. The method includes the steps of providing two components capable of mutual association, one of said components bearing a covalently linked fluorophore; preparing a mixture containing the two components and at least one test substance; irradiating the mixture with polarized light of a suitable wavelength permitting excitation of the fluorophore as indicated by emission of polarized light; measuring the degree of polarization of the emission, and determining the effect of the presence or concentration of the test substance in decreasing the observed emission polarization of a mixture of the two components alone. Inhibitory activity of the test substance correlates with decreased depolarization values.

Abstract: This invention relates to compounds of formula: ##STR1## and pharmaceutically acceptable salts thereof, where A is H, R.sup.1, --CO--R.sup.1 or --CO--OR.sup.1 where R.sup.1 is a substituted or unsubstituted alkyl, heteroalkyl, aryl or heteroaryl group and J is H or NO.sub.2. L-forms of the compounds are currently preferred, although D-forms and racemic mixtures are also encompassed by this invention.