Abstract: The present invention provides methods for treating a subject afflicted with a protein accumulation disease or TBI, comprising administering to the subject at least one compound that increases the level of active cathepsin B in cells of the subject, or a pharmaceutically acceptable salt or ester thereof, in an amount that is effective to treat the subject. The present invention also provides compositions for treating a subject afflicted with a protein accumulation disease or TBI.

Abstract: The present invention provides methods for treating a subject afflicted with a protein accumulation disease or TBI, comprising administering to the subject at least one compound that increases the level of active cathepsin B in cells of the subject, or a pharmaceutically acceptable salt or ester thereof, in an amount that is effective to treat the subject. The present invention also provides compositions for treating a subject afflicted with a protein accumulation disease or TBI.

Abstract: The present invention provides methods for treating a subject afflicted with i) Mild Cognitive Impairment (MCI), ii) early dementia, iii) early ?-synucleinopathy, iv) traumatic brain injury, v) cardiomyopathy, vi) eye disease, or vii) skin damage, comprising administering to the subject at least one compound that increases the level of active cathepsin B in cells of the subject, or a pharmaceutically acceptable salt or ester thereof, in an amount that is effective to treat the subject. The present invention also provides compositions for treating a subject afflicted with i) Mild Cognitive Impairment (MCI), ii) early dementia, iii) early ?-synucleinopathy, iv) traumatic brain injury, v) cardiomyopathy, vi) eye disease, or vii) skin damage.

Abstract: Compounds useful for promoting lysosomal processes and thereby ameliorating the disruption of cellular and functional integrity induced by A? and other protein and glycoconjugate species are provided. Methods for the treatment of neurodegenerative diseases that involve protein accumulation and aggregation in the brain, such as Alzheimer's, Parkinson's and Huntington's Disease, are also provided.

Abstract: The endocannabinoid transporter and FAAH are sites of modulation that allow pharmacological enhancement of protective endocannabinergic signals. Selective inhibitors of the transporter and inhibitors of FAAH caused additive augmentation of endogenous signaling events mediated by the cannabinoid CB1 receptor. Disruption of such signals has been shown to prevent neuronal maintenance processes and increase vulnerability to brain damage. Here, blocking endocannabinoid inactivation enhanced cannabinergic activity and ameliorated cellular disturbances associated with excitotoxicity. Modulating the endocannabinoid system in this way also prevented excitotoxic behavioral abnormalities including memory impairment. Collectively, these results indicate that increasing endocannabinoid responses by inhibiting the endocannabinoid transported and/or the inhibiting FAAH leads to molecular, cellular, and functional protection against excitotoxic insults like stroke and traumatic brain injury.

Abstract: Compounds useful for promoting lysosomal processes and thereby ameliorating the disruption of cellular and functional integrity induced by A? and other protein and glycoconjugate species are provided. Methods for the treatment of neurodegenerative diseases that involve protein accumulation and aggregation in the brain, such as Alzheimer's, Parkinson's and Huntington's Disease, are also provided.

Abstract: Disclosed are compounds and methods of use thereof for modulating lysosome function. Also disclosed is use of the compounds to treat neurodegenerative events and to study lysosomal function.