Activators of integrated stress response pathway for protection against ferroptosis
AssigneeBurke Neurological Institute
InventorRajiv R. Ratan
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Abstract
Methods, agents, and pharmaceutical compositions are provided for treating neurodegenerative disease, for enhancing stroke recovery, and or for inhibiting ferroptosis in a subject. These agents, including 2-deoxyglucose, can be used alone or with the right timing in sequential combination with agents that inhibit the integrated stress response. The present invention addresses these needs and provides methods of treating neurodegenerative conditions, including without the need for dietary restrictions which can be challenging in already unwell patients.
Claims21
A method of treating a neurodegenerative disease in a subject comprising administering directly into the central nervous system (CNS) of the subject an amount of an inhibitor of N-linked glycosylation thereby treating the neurodegenerative disease.
A method of protecting a cell in a subject against ferroptosis comprising administering to the subject an amount of an activator of an Integrated Stress Response pathway effective to increase phosphorylation of a Eukaryotic Initiation Factor 2 alpha (eif2alpha), or to elicit Bdnf gene expression, and thereby reduce ferroptosis, or a method of protecting a cell in a subject against ferroptosis, wherein the subject has, or is experiencing, a neurodegenerative disease comprising administering to the subject an amount of an activator of an Integrated Stress Response pathway effective to increase phosphorylation of an eif2alpha, or to elicit Bdnf gene expression, and thereby reduce ferroptosis.
A method of treating a subject for a stroke, Parkinson's disease, Alzheimer's disease, epilepsy, or Huntington's disease, comprising administering to the subject an amount of an activator of an Integrated Stress Response pathway effective to increase phosphorylation of an eif2alpha so as to treat the stroke, Parkinson's disease, Alzheimer's disease, epilepsy, or Huntington's disease.
21-63. (canceled)
Dependencies are inferred from the claim text.