Inhibitors of mitochondrial fission and methods of use thereof

US8748393B2 · kind B2 · utility

Assignee

• The Board of Trustees of the Leland Stanford Junior University · US

Inventors

• Daria Mochly-Rosen · Menlo Park, US
• Xin QI · Lo Wu, CN
• Nir Qvit · Menlo Park, US

Key dates

• Filing date: May 14, 2012
• Grant date: Jun 10, 2014
• Expiry date: May 14, 2032

Classification

• Technology area (CPC G): Physics
• CPC primary: G01N2500/20
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

The present disclosure provides peptides and constructs that inhibit mitochondrial fission, and compositions comprising the peptides or constructs. The present disclosure provides methods of reducing abnormal mitochondrial fission in a cell. Also provided are methods for designing and validating mitochondrial fission inhibitor constructs and peptides, including but not limited to, evaluating the effects of the constructs and peptides on dynamin 1-like protein (Drp1) guanosine triphosphate phosphatase (GTPase) activity, binding of Drp1 to mitochondrial fission 1 protein (Fis1), reduction of mitochondrial damage, reduction in cell death, inhibition of mitochondrial fragmentation in a cell under pathological conditions, and reduced loss of neurites in primary dopaminergic neurons in a Parkinsonism cell culture.