Title:
INHIBITORS OF MITOCHONDRIAL FISSION AND METHODS OF USE THEREOF
Document Type and Number:
WIPO Patent Application WO/2012/158624
Kind Code:
A3
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 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.
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Inventors:
MOCHLY-ROSEN DARIA (US)
QI XIN (US)
QVIT NIR (US)
QI XIN (US)
QVIT NIR (US)
Application Number:
PCT/US2012/037800
Publication Date:
February 21, 2013
Filing Date:
May 14, 2012
Export Citation:
Assignee:
UNIV LELAND STANFORD JUNIOR (US)
MOCHLY-ROSEN DARIA (US)
QI XIN (US)
QVIT NIR (US)
MOCHLY-ROSEN DARIA (US)
QI XIN (US)
QVIT NIR (US)
International Classes:
A61K38/08; A61K48/00; A61K38/16; A61K38/17; A61K39/395; A61K47/48; A61P25/00; A61P25/28
Foreign References:
| US20080287473A1 | 2008-11-20 |
Other References:
CUI, M. ET AL.: "Perturbations in mitochondrial dynamics induced by human mutant PINK1 can be rescued by the mitochondrial division inhibitor mdivi-1", J. BIOL. CHEM., vol. 285, no. 15, 9 April 2010 (2010-04-09), pages 11740 - 11752
SMIRNOVA, E. ET AL.: "Dynamin-related protein Drp1 is required for mitochondrial division in mammalian cells", MOL. BIOL. CELL, vol. 12, no. 8, August 2001 (2001-08-01), pages 2245 - 2256
DENG, H. ET AL.: "'The Parkinson's disease genes pink1 and parkin promote mitochondrial fission and/or inhibit fusion in Drosophila'", PROC. NATL. ACAD. SCI. USA, vol. 105, no. 38, 23 September 2008 (2008-09-23), pages 14503 - 14508
SMIRNOVA, E. ET AL.: "Dynamin-related protein Drp1 is required for mitochondrial division in mammalian cells", MOL. BIOL. CELL, vol. 12, no. 8, August 2001 (2001-08-01), pages 2245 - 2256
DENG, H. ET AL.: "'The Parkinson's disease genes pink1 and parkin promote mitochondrial fission and/or inhibit fusion in Drosophila'", PROC. NATL. ACAD. SCI. USA, vol. 105, no. 38, 23 September 2008 (2008-09-23), pages 14503 - 14508
Attorney, Agent or Firm:
HARLOCKER, Susan L. et al. (P.O. Box 889Belmont, CA, US)
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