Mitochondria and Oxidative Stress in Neurodegenerative Disorders
Posted December 05, 2007
Our understanding of the interaction of mitochondria with other cellular organelles, with transcription, and in the ability to detect oxidative modification of macromolecules has improved significantly in the past decade. Moreover, the roles of mitochondria and oxidative stress are better defined in the pathophysiology of neurodegenerative disorders.
The goal of a conference held at the Academy from September 26–29, 2007, was to determine what we need to know to move toward better therapies. The conference combined basic, clinical, and translational research in a forum designed to provide the most current information on aspects of mitochondrial function and its relationship to age-related neurodegenerative diseases and their treatment.
The Alzheimer's Association is the leading voluntary health organization in Alzheimer care, support, and research.
American Federation for Aging Research
For 26 years, the American Federation for Aging Research (AFAR) has supported the science of healthier aging. AFAR has played a major role in providing and advancing knowledge of aging and mechanisms of age-related disease by providing start-up grants to more than 2200 early-career scientists.
The Michael J. Fox Foundation for Parkinson's Research
The Michael J. Fox Foundation is dedicated to finding a cure for Parkinson's disease within the decade through an aggressively funded research agenda and to ensuring the development of improved therapies for those living with Parkinson's today.
Mitochondrial Disease information from the Cleveland Clinic
This Web site provides basic information on mitochondrial diseases for the patient population.
Mitochondrial Disorders from the Neuromuscular Disease Center at Washington University
This Web site, in outline form, contains general information about mitochondria as well as detailed information on mitochondrial disorders.
National Parkinson Foundation
NPF is the largest and oldest national Parkinson foundation in the United States. NPF supports Parkinson-related research, patient care, education, training, and outreach.
The United Mitochondrial Disease Foundation
Since 1996, the United Mitochondrial Disease Foundation has funded nearly $5 million in research toward a cure and has helped thousands of families through the family support network. UMDF supports scientific collaboration and family networking through international symposia and is building an endowment to sustain research through the millennium.
Estévez AG, Sahawneh MA, Lange PS, et al. 2006. Arginase 1 regulation of nitric oxide production is key to survival of trophic factor-deprived motor neurons. J. Neurosci. 26: 8512-8516. Full Text
Cochemé HM, Kelso GF, James AM, et al. 2007. Mitochondrial targeting of quinones: therapeutic implications. Mitochondrion 7 Suppl: S94-102.
Cho S, Szeto HH, Kim E, et al. 2007. A novel cell-permeable antioxidant peptide, SS31, attenuates ischemic brain injury by down-regulating CD36. J. Biol. Chem. 282: 4634-4642.
Hurd TR, Prime TA, Harbour ME, et al. 2007. Detection of reactive oxygen species-sensitive thiol proteins by redox difference gel electrophoresis: implications for mitochondrial redox signaling. J. Biol. Chem. 282: 22040-22051.
James AM, Sharpley MS, Manas AR, et al. 2007. Interaction of the mitochondria-targeted antioxidant MitoQ with phospholipid bilayers and ubiquinone oxidoreductases. J. Biol. Chem. 282: 14708-14718.
Krishnan KJ, Reeve AK, Turnbull DM. 2007. Do mitochondrial DNA mutations have a role in neurodegenerative disease? Biochem. Soc. Trans. 35: 1232-1235.Nagai M, Re DB, Nagata T, et al. 2007. Astrocytes expressing ALS-linked mutated SOD1 release factors selectively toxic to motor neurons. Nat. Neurosci. 10: 615-622.
Park CB, Asin-Cayuela J, Camara Y, et al. 2007. MTERF3 is a negative regulator of mammalian mtDNA transcription. Cell 130: 273-285.
Pasinetti GM, Zhao Z, Qin W, et al. 2007. Caloric intake and Alzheimer's disease. Experimental approaches and therapeutic implications. Interdiscip. Top. Gerontol. 35: 159-175.
Perier C, Bove J, Wu DC, et al. 2007. Two molecular pathways initiate mitochondria-dependent dopaminergic neurodegeneration in experimental Parkinson's disease. Proc. Natl. Acad. Sci. USA 104: 8161-8166. Full Text
Ruiz-Pesini E, Lott MT, Procaccio V, et al. 2007. An enhanced MITOMAP with a global mtDNA mutational phylogeny. Nucleic Acids Res. 35: D823-D828. Full Text
Ruiz-Pesini E, Wallace DC. 2006. Evidence for adaptive selection acting on the tRNA and rRNA genes of human mitochondrial DNA. Hum. Mutat. 27: 1072-1081.
Schaefer AM, McFarland R, Blakely EL, et al. 2007. Prevalence of mitochondrial DNA disease in adults. Ann. Neurol. Sep 20; [Epub ahead of print]
Siddiq A, Aminova LR, Ratan RR. 2007. Hypoxia inducible factor prolyl 4-hydroxylase enzymes: center stage in the battle against hypoxia, metabolic compromise and oxidative stress. Neurochem. Res. 32: 931-946.Siddiq A, Ayoub IA, Chavez JC, et al. 2005. Hypoxia-inducible factor prolyl 4-hydroxylase inhibition. A target for neuroprotection in the central nervous system. J. Biol. Chem. 280: 41732-41743. Full Text
Szeto HH. 2006. Mitochondria-targeted peptide antioxidants: novel neuroprotective agents. AAPS J. 8: E521-E531. Full Text
Taylor RW, Turnbull DM. Mitochondrial DNA transcription: regulating the power supply. Cell 2007 130: 211-213.
Thomas DA, Stauffer C, Zhao K, et al. 2007. Mitochondrial targeting with antioxidant peptide SS-31 prevents mitochondrial depolarization, reduces islet cell apoptosis, increases islet cell yield, and improves posttransplantation function. J. Am. Soc. Nephrol. 18: 213-222.
Tong JJ, Schriner SE, McCleary D, et al. 2007. Life extension through neurofibromin mitochondrial regulation and antioxidant therapy for neurofibromatosis-1 in Drosophila melanogaster. Nat. Genet. 39: 476-485.
Wang J, Ho L, Chen L, et al. 2007. Valsartan lowers brain beta-amyloid protein levels and improves spatial learning in a mouse model of Alzheimer disease. J. Clin. Invest. Oct 25; [Epub ahead of print]. Full Text
Wang J, Ho L, Zhao Z, et al. 2006. Moderate consumption of Cabernet Sauvignon attenuates Abeta neuropathology in a mouse model of Alzheimer's disease. FASEB J. 20: 2313-2320.
Wu DC, Re DB, Nagai M, et al. 2006. The inflammatory NADPH oxidase enzyme modulates motor neuron degeneration in amyotrophic lateral sclerosis mice. Proc. Natl. Acad. Sci. USA 103: 12132-12137. Full Text
Gary E. Gibson, PhD
Gary Gibson is a tenured professor of neuroscience at Weill Medical College of Cornell University and at Burke Medical Research Institute. Gibson is also a member of the graduate program in neuroscience at Cornell Medical College and teaches graduate students in that program.Gibson received his PhD in physiology with emphasis in biochemistry and neuroscience at Cornell University. He did his postdoctoral work at UCLA, where he became a faculty member. He then moved to Cornell University Medical College and Burke Medical Research Institute where he has been ever since. He also served as the associate director of the Dementia Research Service.
Gibson received the American Society for Neurochemistry award for outstanding young investigator. He has given lectures at many institutions and honorary lectures including the Deans hour at Cornell University Medical College, the NIH Director's Talk, and the Visek Lectureship at the University of Illinois. He has served on over 20 NIH review panels for reviewing grants. He regularly reviews grants for the Alzheimer Association and the American Federation for Aging Research. He is a member of numerous scientific societies including the American Society for Neurochemistry (past secretary, 2005–2006), the Society for Neuroscience, the International Society for Neurochemistry, the International Society for Cerebral Blood Flow and Metabolism, the American Institute of Nutrition, and the American Society for Pharmacology and Experimental Therapeutics.
Rajiv R. Ratan, MD, PhD
Rajiv Ratan is the director of the Burke/Cornell Medical Research Institute. He is also Burke Professor of Neurology, Neuroscience, and Rehab Medicine at the Weill Medical College of Cornell University. Ratan received his MD and PhD in pharmacology from New York University where he was awarded the John Woodruff Simpson Fellowship in Medicine from Amherst College, was a National Institutes of Health-MSTP Fellow, and a member of the Alpha Omega Alpha Honor Medical Society.
After completing an internship in Medicine at the University of Chicago Hospitals and Clinics, Ratan joined the Johns Hopkins Hospital, where he was a neurology resident and chief neurology resident in the Department of Neurology, and a fellow in rehabilitation in the Department of Rehabilitation Medicine and the Department of Neuroscience. At Johns Hopkins, he was awarded the Jay Slotkin Award for Excellence in Research and the Passano Foundation Clinician Scientist Award. From 1994 to 1996 Ratan was an assistant professor in the Departments of Neurology and Physical Medicine and Rehabilitation at the Johns Hopkins University School of Medicine. In 1996 Ratan joined the staff of Harvard Medical School and Beth Israel Hospital as an assistant professor and later an associate professor in the Department of Neurology.
Ratan is a member of the Board of Directors of both the Burke Rehabilitation Hospital and the Boston ALS Therapy Alliance. He is also a member of the Scientific Advisory Board of the Boston Cure Project. Ratan is on several editorial boards.
M. Flint Beal, MD
M. Flint Beal is the Anne Parrish Titzell Professor and Chairman of the Department of Neurology and Neuroscience at the Weill Medical College of Cornell University and Director of the Neurology service at the New York Presbyterian Cornell Campus. Beal received his medical degree from the University of Virginia in 1976 and did his internship and first year residency in Medicine at New York–Cornell before completing his residency in Neurology at The Massachusetts General Hospital. He joined the neurology faculty at Harvard in 1983. Beal was professor of neurology at the Harvard Medical School and chief of the neurochemistry laboratory at Massachusetts General Hospital before moving to Cornell.
Beal is the author or coauthor of more than 300 scientific articles and more than 125 books, book chapters and reviews. He serves on the editorial boards of seven journals. Beal is a member of the Alpha Omega Alpha Medical Honorary Society and received the Derek Denny-Brown Neurological Scholar Award of the American Neurologic Association. He has served on the Council of the American Neurologic Association and on the Science Advisory Committees of the Hereditary Disease Foundation, Huntington's Disease Society of America, Parkinson's Disease Study Group, Parkinson's Disease Foundation, Bachman-Strauss Foundation, the ALS Association, and the American Health Assistance Foundation. Beal is also a member of the Institute of Medicine of the National Academy of Sciences.
Douglas Wallace, PhD
Douglas Wallace is the Donald Bren Professor of Molecular Medicine and the director for the Center for Molecular and Mitochondrial Medicine and Genetics at the University of California, Irvine. Wallace received his PhD in microbiology and human genetics from Yale University in 1975. In 1976 he became an assistant professor of genetics at the Stanford University School of Medicine. He left Stanford in 1983 to join the faculty of Emory University in Atlanta, where he was the director for the Center for Molecular Medicine. In 2002 he left Emory University and joined the University of California, Irvine. He was elected as a member of the American Academy of Arts and Sciences in 2004.
Wallace has been a pioneer in the study of human mitochondrial genetics and the role of mitochondrial DNA (mtDNA) variation in human evolution and disease. Together with his colleagues, he defined the basic principles of human mitochondrial genetics, and then surveyed human mtDNA variation from around the world, permitting the reconstruction of ancient human origins and migrations. Concurrently, Wallace and his colleagues investigated the role of mtDNA variation in human disease, leading to the discovery of the first inherited mtDNA disease mutation and the demonstration of the importance of mtDNA variation in aging and degenerative diseases.
Doug M. Turnbull, MD, PhD
Doug Turnbull is professor of neurology at the University of Newcastle upon Tyne. Turnbull is a clinical neurologist with a specific interest in mitochondrial genetics. His main research involves the clinical aspects, diagnosis and management of mitochondrial DNA disease, as well as trying to understand the involvement of the mitochondrial genome in ageing and cancer.
Conrad C. Alano, PhD
Maria Ankarcrona, PhD
Joseph S. Beckman, PhD
Sarah B. Berman, MD, PhD
Paolo Bernardi, MD
John P. Blass, MD, PhD
Ella Bossy-Wetzel, PhD
Susan E. Browne, PhD
Roderick A. Capaldi, DPhil
Juan C. Chavez, PhD
Christos Chinopoulos, MD, PhD
Valina L. Dawson, PhD
Gerald Dienel, PhD
Robert J. Ferrante, PhD
Gary Fiskum, PhD
J. Timothy Greenamyre, MD, PhD
Claire Henchcliffe, MD, DPhil
Johannes M. Herrmann, PhD
Jeffrey A. Johnson, PhD
Mariusz Karbowski, PhD
Michael T. Lin, MD
Dong Liu, MD, PhD
Carmen A. Mannella, PhD
Lisa Mosconi, PhD
Mike Murphy, PhD
David G. Nicholls, PhD
Giulio Maria Pasinetti, MD, PhD
Domenico Praticò, MD
Serge Przedborski, MD, PhD
Rosario Rizzuto, MD, PhD
Herminia Diana Rosas, MD
Richard C. Scarpulla, PhD
Bruce Spiegelman, PhD
Anatoly Starkov, PhD
Hazel H. Szeto, MD, PhD
Andre Terzic, MD, PhD
Nicholas K. Tonks, PhD
Nicholas W. Wood, MB, ChB, PhD
Xiongwei Zhu, PhD
Alan Dove is a science writer and reporter for Nature Medicine, Nature Biotechnology, and Bioscience Technology. He also teaches at the NYU School of Journalism, and blogs at http://dovdox.com.
This conference has been made possible in part by grants from:
Mr. and Mrs. William Littleford