Environmental Factor, November 2009, National Institute of Environmental Health Sciences
First Annual Meeting of the NIEHS Centers for Neurodegeneration Science
By Dixie Ann Sawin
The NIEHS Centers for Neurodegeneration Science (CNS) - formerly The Collaborative Centers for Parkinson's Disease Environmental Disease Research (CCPDER) - held the program's first annual meeting on October 8 and 9 at NIEHS. Speakers included scientists from the centers at Emory University, The Burnham Institute and the University of California, Los Angeles (UCLA), as well as investigators with the NIEHS Intramural program and the National Toxicology Program (NTP). NIEHS Health Science Administrator Cindy Lawler, Ph.D., is the extramural officer who oversees the NIEHS-funded centers.
The goals of the meeting included fostering interaction among the centers that could lead to collaborative research, highlighting the findings of all the Centers, enabling trainees to become more integrated within the program, and introducing center investigators to NIEHS investigators involved in related research (see text box). As Lawler observed, interaction of trainees across centers is "a key part of the program."
The CNS program addresses the need for integrated research efforts involving basic and clinical scientists in a quest to discover the causes of and possible treatments for neurodegenerative diseases. In 2008, NIEHS awarded five-year CNS grants totaling $4.2 million per year to Emory, UCLA and Burnham. Each Center supports an administrative core, service/facility cores and a research development core for pilot projects by investigators studying Parkinson's Disease (PD).
According to NIEHS Acting Deputy Director Steve Kleeberger, Ph.D., NIEHS has a significant commitment to this type of research on neurodegenerative disease and supports more than 20 individual RO1 and R25 grants on PD, ranging from the epidemiology of PD to the development of new animal models of PD and studies of brain transport and regenerative mechanisms. "These Centers are especially important for helping move this research forward," Kleeberger stressed, "and the interaction between multiple disciplines within the centers... is a really important mechanism to enable the kind of research necessary to understand the pathogenesis of disease."
The Emory group started off the presentations on the first day with an overview by Center Director Gary Miller, Ph.D. The overall goals of this Center are to determine how environmental and genetic disruption of dopamine (DA) storage leads to oxidative damage; to identify novel mechanisms by which DA neurons respond to oxidative stress; to determine how environmental toxicants disrupt redox balance; and to identify novel biomarkers of environmental toxicant exposure associated with PD.
The overall goals of the Burnham investigators were outlined by Center Director Stuart Lipton, M.D., Ph.D. His group focuses on the ability of S-nitrosylation and oxidation of proteins to mimic genetic mutations seen in PD. These mutations cause protein mis-folding, abnormal signaling and eventual cell injury and death. Lipton's group proposes to generate "novel hits" from chemical library screens that could possibly be used as targets for therapeutic intervention.
The UCLA researchers, headed by Marie-Fran��oise Chesselet, M.D., Ph.D., seek to identify novel mechanisms that contribute to the pathogenesis of sporadic PD by investigating primary cellular pathways affected by agricultural pesticide use, particularly in the well-characterized patient cohort in the agricultural region of the California Central Valley. Initial evidence suggests that pesticides lead to aberrant folding of proteins and the involvement of the ubiquitin-proteasome system (UPS), adverse effects on microtubule assembly and inhibition of aldehyde dehydrogenase - an important detoxification enzyme. The overall objective is to determine whether disruption of these processes can increase the risk of developing PD.
A poster session featuring the work from the different laboratories within each center was held after the first day of talks. A trainee meeting, organized by NIEHS Health Science Administrator Mike Humble, Ph.D., provided useful information on training and career development.
(Dixie-Ann Sawin, Ph.D., is a post-doctoral research fellow in the NIEHS Laboratory of Neurobiology Neurotoxicology Group on detail as a writer for the Environmental Factor.)
The Intramural Perspective
Several Intramural scientists attended the CNS meeting and interacted with the CNS grantees. They were also interested in the poster presentations by investigators and trainees.
On the second day of the CNS meeting, NIEHS and NTP investigators presented their work. Jau-Shyong Hong, Ph.D., head of the Pharmacology Group, and G. Jean Harry, Ph.D., head of the Neurotoxicology Group, shed light on the neurotoxic and neuroprotective effects of microglia, the brain macrophage cells, and their putative role in PD.
Raymond Tice, Ph.D, chief of the NTP Biomolecular Screening group highlighted the goals of the Tox21 Community and the pursuit of molecular biomarkers of exposure to drugs or toxicants.
Epidemiology Branch Staff Scientist Freya Kamel, Ph.D, and Tenure Track Investigator Honglei Chen, M.D., Ph.D, highlighted their studies of the associations of pesticides and smoking with PD development.