UTSW researchers identify unique peptide with therapeutic potential against cancers, neurological disorders, and infectious diseases
DALLAS - Feb. 7, 2013 - UT Southwestern Medical Center scientists
have synthesized a peptide that shows potential for pharmaceutical development into agents for treating infections, neurodegenerative
disorders, and cancer through an ability to induce a cell-recycling process called autophagy.
Autophagy is a fundamental recycling process in which intracellular enzymes digest unneeded and broken parts of the cell into
their individual building blocks, which are then reassembled into new parts. The role of autophagy is crucial both in keeping
cells healthy and in enabling them to fight different diseases. Physician scientists in UT
Southwestern's Center for Autophagy Research are deciphering how to manipulate the autophagy process in an effort to disrupt the progression of disease and promote health.
In their latest findings reported online in the journal Nature, Center researchers were able to synthesize a peptide
called Tat-beclin 1, which induces the autophagy process. Mice treated with Tat-beclin-1 were resistant to several infectious
diseases, including West Nile virus and another mosquito-borne virus called chikungunya that is common to Asia, Africa, and
India. In additional experiments, the team demonstrated that human cells treated with the peptide were resistant to HIV
infection in a laboratory setting.
"Because autophagy plays such a crucial role in regulating disease, autophagy-inducing agents such as the Tat-beclin 1 peptide may have potential for pharmaceutical development and the subsequent prevention and treatment of a broad range of human diseases," said Dr. Beth Levine , Director of the Center for Autophagy Research and senior author of the study. Dr. Levine, Professor of Internal Medicine and Microbiology, is a Howard Hughes Medical Institute investigator at UT Southwestern.
Disruption of the autophagy process is implicated in a wide variety of conditions including aging, and diseases, including cancers, neurodegenerative diseases such as Parkinson's and Alzheimer's, and infectious diseases such as those caused by West Nile and HIV viruses.
UT Southwestern has applied for a patent on Tat-beclin-1. Peptides are strings of amino acids found in proteins. The Tat-beclin 1 peptide was derived from sequences in beclin 1, one of the first known proteins in mammals found to be essential for autophagy, a finding that was made by Dr. Levine's laboratory. Her research has since demonstrated that defects in beclin 1 contribute to many types of disease. Conversely, beclin 1 activity and the autophagy pathway appear to be important for protection against breast, lung, and ovarian cancers, as well as for fighting off viral and bacterial infections, and for protecting individuals from neurodegenerative diseases and aging.
The study was supported by grants from the National Institutes of Health, the National Science Foundation, the HHMI, the Netherlands Organization
for Scientific Research-Earth and Life Sciences Open Program, Cancer Research United Kingdom, and a Robert A. Welch Foundation Award.
Other UT Southwestern scientists involved include Dr. Sanae Shoji-Kawata, first author and former postdoctoral researcher now
in Japan; Dr. Rhea Sumpter Jr., an
instructor of internal medicine and member of the autophagy center; Dr. Matthew Leveno, assistant
professor of internal medicine and autophagy center member; Dr. Carlos Huerta, former postdoctoral researcher of biochemistry now at
Reata Pharmaceuticals; Dr. Nick Grishin, professor
of biochemistry and HHMI investigator; Dr. Lisa Kinch, bioinformatics scientist; Zhongju Zou, research specialist; and Quhua Sun,
Researchers from the University of California, San Diego; Rady Children's Hospital-San Diego; Baylor College of Medicine
in Houston; Washington University School of Medicine in St. Louis; Utrecht University, Utrecht, The Netherlands; Cancer Research UK,
London; Massachusetts General Hospital, Harvard Medical School; the Broad Institute of Harvard and Massachusetts Institute of
Technology; Columbia University College of Physicians and Surgeons; the HHMI; and University of California, Berkeley, also
participated in the study.
About UT Southwestern Medical Center
UT Southwestern, one of the premier medical centers in the nation, integrates pioneering biomedical research with
exceptional clinical care and education. The institution's faculty has many distinguished members, including
five who have been awarded Nobel Prizes since 1985. Numbering more than 2,700, the faculty is responsible
for groundbreaking medical advances and is committed to translating science-driven research quickly to
new clinical treatments. UT Southwestern physicians provide medical care in 40 specialties to more
than 100,000 hospitalized patients and oversee nearly 2 million outpatient visits a year.
SOURCE: UT Southwestern Medical Center
Reproduced with permission - "UT Southwestern Medical Center"
UT Southwestern Medical Center
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