Abstract: Ferroptosis (cell death mediated by iron-dependent lipid peroxide accumulation) results from lipid peroxidation of phospholipids containing polyunsaturated fatty acyl moieties. Glutathione, the key cellular antioxidant capable of inhibiting lipid peroxidation via the activity of the enzyme glutathione peroxidase 4 (GPX-4), is generated directly from the sulfur-containing aminoacid cysteine, and indirectly from methionine via the transsulfuration pathway. Cysteine and methionine deprivation (CMD) in the diet can synergistically increase RSL3-mediated cell death and lipid peroxidation in both murine and human glioma cell lines and in ex-vivo organotypic slice cultures. A cysteine-depleted, methionine-restricted diet can improve survival in an syngeneic orthotopic murine glioma model. This CMD diet leads to profound in-vivo metabolomic, proteomic and lipidomic alterations, leading to improvements in the efficacy of ferroptotic therapies in glioma treatment with a non-invasive dietary modification.

Abstract: The invention is directed to methods for in vivo amplification of neural progenitor cells using the proliferative environment of glial neoplasms in adult brain. The progenitor cells have the capacity to proliferate and differentiate into mature brain cells which can be used for cell replacement therapies. The invention also provides cell replacement therapy methods for treating central nervous system diseases or injuries, including multiple sclerosis, stroke, Alzheimer's disease and Parkinson's disease.

Abstract: The invention provides antagonists and agonists of dynein mediated activity, for example specific inhibitory RNAs and dominant negative cDNAs which function as antagonists of LIS1 and dynein, and compositions comprising such antagonist and agonists. Provided are also methods for treating unwanted cell proliferation of neural progenitor cells such as cancers of the CNS, including gliomas, by administering the antagonists of the invention.