Abstract: Compounds that modulate mitochondrial reactive oxygen species (ROS) production are provided. The compounds may modulate ROS production at defined sites without also altering energy production. Methods of using and identifying such compounds are also provided.

Abstract: This invention provides novel caspase inhibitors useful for prophylaxis or treatment of a number of pathologies, including, for example, Huntington's disease. In certain embodiments the inhibitors include inhibitors of casepase-3 and/or casepase-6.

Abstract: The invention provides methods and compositions for reducing or inhibiting net beta-amyloid peptide production and/or amyloid plaque formation. The methods and compositions involve administering a netrin-1 polypeptide or netrin-1 therapeutic to a subject in need thereof.

Abstract: The invention provides compositions and methods for the treatment of mild cognitive impairment (MCI), and for inhibiting, reducing, delaying and/or preventing the progression of MCI to Alzheimer's disease. The methods entail administering an effective amount of one or more compounds selected from the group consisting of tropisetron, disulfuram, honokiol and nimetazepam. The methods also are useful for prophylactic and therapeutic treatment of amyloidogenic diseases, including Alzheimer's disease.

Abstract: This invention provides a novel screening system for identifying p53 mimetics/agonists. Also provided are small organic molecules that act as effective p53 mimetics/agonists.

Abstract: The present invention is directed to compounds and methods for treating a mammal exposed to Francisella tularensis.

Abstract: This invention pertains to the identification of neurogenerative and/or neurotrophic factors that can induce migration of stem cells to neural tissue and/or induce proliferation and/or differentiation of such cells into neurons. Such agents include, but are not limited to stem cell factor (SCF), heparin binding EGF (HB-EGF), and VEGF.

Abstract: The invention provides a method for reducing or inhibiting net beta-amyloid peptide production and amyloid plaque formation associated with Alzheimer's Disease by administering to a subject an amount of a netrin-1 polypeptide, wherein the netrin-1 polypeptide comprises an amino acid sequence that a) binds to a naturally occurring APP protein and b) inhibits A? peptide production. A netrin-1 polypeptide has an amino acid sequence sufficient for specific binding of the netrin-1 polypeptide to the APP protein. A netrin-1 polypeptide can mimic netrin-1-mediated signal transduction by altering the localization, protein-protein binding and/or enzymatic activity of an intracellular protein involved in an APP signal pathway.

Abstract: In accordance with the present invention, it is demonstrated that selected mutations such as an Asp->Ala (D664A) mutation in APP (which prevents cleavage at the caspase cleavage site) prevent both hippocampal synaptic loss and dentate gyral atrophy, even though such mutations do not interfere with the production of A? or the formation of amyloid plaques in a transgenic model of Alzheimer's disease. Accordingly, in view of this finding, methods have been developed for the identification of agents which block cleavage at Asp664 of APP, including transgenic animals which are useful for such purpose, as well as methods for the use thereof for the treatment of neurodegenerative diseases.

Abstract: The invention is directed to a method of identifying a compound that modulates SP-induced paraptosis by (a) contacting a population of cells with an effective amount of substance P to induce SP-induced paraptosis; (b) contacting a first sub-population of the cells with a test-compound, and a second sub-population of the cells with a control-compound; and (c) comparing the amount of cell death between the first and second sub-populations of cells, where a difference in the amount of cell death between the first and second sub-populations of cells indicates that the test-compound is a compound that modulates SP-induced paraptosis. The invention is also directed to a method of treating a condition associated with excessive cell accumulation by administering to a subject in need of such treatment an effective amount of a compound identified from the method described above where the effective amount of the compound increases SP-induced paraptosis.

Abstract: This invention pertains to the discovery that elevated level of free iron causal in the onset and/or progression of diseases characterized by neural degeneration (e.g., Parkinson's Disease). It was also discovered that lowering free iron levels can inhibit (e.g. reduce or eliminate) the onset and/or progression of one or more symptoms of such diseases. Thus, in one embodiment this invention provides a method of inhibiting neural degeneration in a mammal. The method involves reducing free iron levels in a neural tissue of said animal in an amount sufficient to inhibit neural degeneration in said neural tissue.

Abstract: Mitochondrial targets for drug screening assays and for therapeutic intervention in the treatment of diseases associated with altered mitochondrial function are provided. Complete amino acid sequences [SEQ ID NOS:1-3025] of polypeptides that comprise the human heart mitochondrial proteome are provided, using fractionated proteins derived from highly purified mitochondrial preparations, to identify previously unrecognized mitochondrial molecular components.