INHIBITORS OF MITOCHONDRIAL FISSION AND METHODS OF USE THEREOF

摘要

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 Drp1 GTPase activity, binding of Drp1 to 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.

主权项

1. A mitochondrial fission inhibitor peptide consisting of 7, 8 or 9 amino acids,
wherein the inhibitor peptide comprises an amino acid sequence which is 7 amino acids in length and which comprises the amino acid sequence as set forth in SEQ ID NO:12 having one, two or three conservative amino acid substitutions.