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The NINDS supports a broad range of studies aimed at discovering the cause(s) of Parkinson's disease, finding better treatments, and ultimately preventing and curing the disorder. In 2000 a working group established the Parkinson’s Disease Research Agenda initiating a planning process to ensure that extraordinary opportunities to move toward a cure are adequately supported and that critical obstacles to progress are addressed. In 2002 a Summit was convened to gain a better sense of where the field of PD research stands internationally, and to collect information on the "roadblocks" that may still be impacting progress. This led to the development of the Parkinson’s Matrix which identifies additional goals that can help facilitate PD research.
This NIH disease specific web site was developed to facilitate research efforts on Parkinson’s Disease, track the progress of the PD Research agenda and Matrix activities, and provides both the research and lay community with information and resources. The Parkinson's disease research portfolio is managed by the NINDS Neurodegeneration Group. Highlights:Updated August 27, 2004 |
Parkinson's Funding Quick LinksEvents and Other ActivitiesResearch Newsa-Synuclein promoter confers susceptibility to Parkinson's disease
Ann of Neurol, 2004; 56 (4): 591–595
Familial Parkinson's disease (PD) has been linked to missense and genomic multiplication mutations of the -synuclein gene (SNCA). Genetic variability within SNCA has been implicated in idiopathic PD in many populations. We now confirm and extend these findings, within a Belgian sample, using a high-resolution map of genetic markers across the SNCA locus. Our study implicates the SNCA promoter in susceptibility to PD, and more specifically defines a minimum promoter haplotype, spanning approximately 15.3kb of sequence, which is overrepresented in patients. Our findings represent a biomarker for PD and may have implications for patient diagnosis, longitudinal evaluation, and treatment.
Double knockout mice for a- and b-synucleins: Effect on synaptic functions
PNAS October 12, 2004; 10 (41): 14966–14971
An abundant presynaptic protein, a-synuclein, is centrally involved in the pathogenesis of Parkinson’s disease. However, conflicting data exist about the normal function of a-synuclein, possibly because a-synuclein is redundant with the very similar b-synuclein. To investigate the functions of synucleins systematically, we have now generated single- and double-knockout (KO) mice that lack a- and/or b-synuclein. We find that deletion of synucleins in mice does not impair basic brain functions or survival. We detected no significant changes in the ultrastructure of synuclein-deficient synapses, in short- or long-term synaptic plasticity, or in the pool size or replenishment of recycling synaptic vesicles. However, protein quantitations revealed that KO of synucleins caused selective changes in two small synaptic signaling proteins, complexins and 14-3-3 proteins. Moreover, we found that dopamine levels in the brains of double-KO but not single-KO mice were decreased by ~20%. In contrast, serotonin levels were unchanged, and dopamine uptake and release from isolated nerve terminals were normal. These results show that synucleins are not essential components of the basic machinery for neurotransmitter release but may contribute to the long-term regulation and/or maintenance of presynaptic function.
Derivation of midbrain dopamine neurons from human embryonic stem cell
PNAS August 24, 2004; 101 (34): 12543–12548
Human embryonic stem (hES) cells are defined by their extensive self-renewal capacity and their potential to differentiate into any cell type of the human body. The challenge in using hES cells for developmental biology and regenerative medicine has been to direct the wide differentiation potential toward the derivation of a specific cell fate. Within the nervous system, hES cells have been shown to differentiate in vitro into neural progenitor cells, neurons, and astrocytes. However, to our knowledge, the selective derivation of any given neuron subtype has not yet been demonstrated. Here, we describe conditions to direct hES cells into neurons of midbrain dopaminergic identity. Neuroectodermal differentiation was triggered on stromal feeder cells followed by regional specification by means of the sequential application of defined patterning molecules that direct in vivo midbrain development. Progression toward a midbrain dopamine (DA) neuron fate was monitored by the sequential expression of key transcription factors, including Pax2, Pax5, and engrailed-1 (En1), measurements of DA release, the presence of tetrodotoxin-sensitive action potentials, and the electron-microscopic visualization of tyrosinehydroxylase-positive synaptic terminals. High-yield DA neuron derivation was confirmed from three independent hES and two monkey embryonic stem cell lines. The availability of unlimited numbers of midbrain DA neurons is a first step toward exploring the potential of hES cells in preclinical models of Parkinson’s disease. This experimental system also provides a powerful tool to probe the molecular mechanisms that control the development and function of human midbrain DA neurons.
News Archive
Reviewed October 12, 2004 |
