eBriefing

Anatomy of a Tremor: On the Molecular Basis of Parkinson's Disease

Anatomy of a Tremor
Reported by
Don Monroe

Posted May 19, 2006

Overview

Perhaps a million people in the United States endure Parkinson's disease, which becomes increasingly common with age. Among neurodegenerative diseases, only Alzheimer's disease is more prevalent. The symptoms of Parkinson's disease, which include resting tremor, rigidity, slowed movement, and postural instability, can be controlled with drugs, but this approach becomes ineffective over time. Improved treatment of Parkinson's disease will likely require deeper understanding of the molecular events involved. Three leading researchers discussed this approach at a December 8, 2005, symposium of the New York Academy of Sciences' Neurodegenerative Diseases Discussion Group.

Web Sites

General Information and Research

Awakenings
An informational site on Parkinson's disease for patients, primary care physicians, and specialists.

MedlinePlus
Offers an extensive set of articles offering news and basic information about Parkinson's disease.

National Institute of Neurological Disorders and Stroke
The National Institutes of Health page dedicated to Parkinson's disease offers numerous information sheets and news on developing research and conferences. More information for researchers is available at the Parkinson's Disease Research Web.

Foundations

American Parkinson Disease Association
This organization offers information for patients and physicians, and funds grants for promising research to find a cure for Parkinson's disease.

The Michael J. Fox Foundation for Parkinson's Research
The largest nonprofit funder of Parkinson's research.

The National Parkinson Foundation (NPF)
Supports Parkinson-related research, patient care, education, training, and outreach.

Parkinson's Disease Foundation
A national non-profit organization devoted to funding research, providing education, and advocating for Parkinson's disease. Information about different types of grants and fellowships for research is also available online.


Books

Langston, J. W. & J. Palfreman. 1996. The Case of the Frozen Addicts. New York, Pantheon.
Amazon | Barnes & Noble
This popular account describes the discovery of Parkinson's symptoms in users of synthetic heroin contaminated with MPTP.

Sacks, O. 1990. Awakenings. New York, Vintage.
Amazon | Barnes & Noble
A gripping account of the promise and eventual disappointment of L-dopa treatment of victims of post-encephalitic Parkinson's disease.


Journal Articles

Parkinson's Disease: Mechanisms and Models

Benner, E. J., R. L. Mosley, C. J. Destache, et al. 2004. Therapeutic immunization protects dopaminergic neurons in a mouse model of Parkinson's disease. Proc. Natl. Acad. Sci. USA 101: 9435-9440. Full Text

Chung K. K., B. Thomas, X. Li, et al. 2004. S-nitrosylation of parkin regulates ubiquitination and compromises parkin's protective function. Science 304: 1328-1331.

Cuervo, A. M., L. Stefanis, R. Fredenburg, et al. 2004. Impaired degradation of mutant alpha-synuclein by chaperone-mediated autophagy. Science 305: 1292-1295.

Dauer, W. & S. Przedborski. 2003. Parkinson's disease: mechanisms and models. Neuron 39: 889-909.

Jackson-Lewis V., M. Jakowec, R. E. Burke & S. Przedborski. 1995. Time course and morphology of dopaminergic neuronal death caused by the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Neurodegeneration 4: 257-269.

Liberatore, G. T., V. Jackson-Lewis, S. Vukosavic, et al. 1999. Inducible nitric oxide synthase stimulates dopaminergic neurodegeneration in the MPTP model of Parkinson disease. Nat Med. 5: 1403-1409.

Pennathur, S., V. Jackson-Lewis, S. Przedborski & J. W. Heinecke. 1999. Mass spectrometric quantification of 3-nitrotyrosine, ortho-tyrosine, and o,o'-dityrosine in brain tissue of 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine-treated mice, a model of oxidative stress in Parkinson's disease. J. Biol. Chem. 274: 34621-43628. Full Text

Perier C., K. Tieu, C. Guegan, et al. 2005. Complex I deficiency primes Bax-dependent neuronal apoptosis through mitochondrial oxidative damage. Proc. Natl. Acad. Sci. USA 102: 19126-19131. Epub 2005 Dec 19.

Przedborski, S., Q. Chen, M. Vila, et al. 2001. Oxidative post-translational modifications of alpha-synuclein in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of Parkinson's disease. J. Neurochem. 76: 637-640.

Tieu, K., C. Perier, C. Casperson, et al. 2003. D-β-hydroxybutyrate rescues mitochondrial respiration and mitigates features of Parkinson disease. J. Clin. Invest. 112: 892-901. Full Text

Vila, M. & S. Przedborski. 2003. Targeting programmed cell death in neurodegenerative diseases. Nat. Rev. Neurosci. 4: 365-375.

Wu, D. C., P. Teismann, K. Tieu, et al. 2003. NADPH oxidase mediates oxidative stress in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinson's disease. Proc. Natl. Acad. Sci. USA 100: 6145-6150. Full Text

Wu, D. C., V. Jackson-Lewis, M. Vila, et al. 2002. Blockade of microglial activation is neuroprotective in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson disease. J. Neurosci. 22: 1763-1771. Full Text

Structural Properties and Interactions of the Parkinson's and Alzheimer's Proteins Synuclein and Tau

Bussell, R. Jr. & D. Eliezer. 2004. Effects of Parkinson's disease-linked mutations on the structure of lipid-associated α-synuclein. Biochemistry 43: 4810-4818.

Bussell, R. Jr & D. Eliezer. 2003. A structural and functional role for 11-mer repeats in alpha-synuclein and other exchangeable lipid binding proteins. J. Mol. Biol. 329: 763-778.

Bussell, R. Jr. & D. Eliezer. 2001. Residual structure and dynamics in Parkinson's disease-associated mutants of α-synuclein. J. Biol. Chem. 276: 45996-46003. Full Text

Bussell, R. Jr., T. F. Ramlall & D. Eliezer. 2005. Helix periodicity, topology, and dynamics of membrane-associated α-synuclein. Protein Sci. 14: 862-872. Full Text

Davidson W. S., A. Jonas, D. F. Clayton & J. M. George 1998. Stabilization of α-synuclein secondary structure upon binding to synthetic membranes. J. Biol Chem. 273: 9443-9449. Full Text

Eliezer, D., E. Kutluay, R. Bussell Jr. & G. Browne. 2001. Conformational properties of α-synuclein in its free and lipid-associated states. J. Mol. Biol. 307: 1061-1073.

Eliezer, D., P. Barre, M. Kobaslija, et al. 2005. Residual structure in the repeat domain of tau: echoes of microtubule binding and paired helical filament formation. Biochemistry 44: 1026-1036.

Genetic and Molecular Effectors of α-Synuclein Aggregation Involved in Parkinson's Disease

Giasson, B. I., J. E. Duda, S. M. Quinn, et al. 2002. Neuronal α-synucleinopathy with severe movement disorder in mice expressing A53T human α-synuclein. Neuron 34: 521-533.

Giasson, B. I., M. S. Forman, M. Higuchi, et al. 2003. Initiation and synergistic fibrillization of tau and α-synuclein. Science 300: 636-640.

Liu, C. W., B. I. Giasson, K. A. Lewis, et al. 2005. A precipitating role for truncated α-synuclein and the proteasome in α-synuclein aggregation: implications for pathogenesis of Parkinson disease. J. Biol. Chem. 280: 22670-22678. Full Text

Yazawa, I., B. I. Giasson, R. Sasaki, et al. 2005. Mouse model of multiple system atrophy α-synuclein expression in oligodendrocytes causes glial and neuronal degeneration. Neuron 45: 847-859.

Speakers

Serge Przedborski, MD, PhD

Columbia University
email | web site | publications

Serge Przedborski is the William Black Professor of Neurology and a professor of pathology at Columbia University's College of Physicians and Surgeons in New York. He received his MD degree from the Université Libre de Bruxelles (ULB), Belgium. He did his internship and residency in neurology and psychiatry at the ULB-Erasme Medical Center, Belgium. He received his PhD degree in neurological sciences from ULB School of Medicine, Belgium. His postdoctoral research was done at Columbia University, where he became assistant professor of neurology in 1991.

David Eliezer, PhD

Weill Medical College of Cornell University
email | web site | publications

David Eliezer is associate professor of biochemistry and of the program in structural biology at the Weill Medical College of Cornell University. He received a PhD in physics from Stanford University in 1994, where he studied protein folding kinetics. Before moving to Cornell, he was a postdoctoral fellow at the Scripps Research Institute, where he used high resolution NMR spectroscopy to probe structure in highly and partially unfolded states of proteins.

Benoit Giasson, PhD

University of Pennsylvania
email | web site | publications

Benoit Giasson is an assistant professor of pharmacology at the University of Pennsylvania. He received a PhD in 1997 from McGill University, Montreal, Canada.


Don Monroe

Don Monroe is a science writer based in Murray Hill, New Jersey. After getting a PhD in physics from MIT, he spent more than fifteen years doing research in physics and electronics technology at Bell Labs. He writes on biology, physics, and technology.