Parkinson's disease: medicines are just around the corner?
Parkinson's disease, or trembling paralysis, is a neurodegenerative disease that affects dopamine neurons in the brain and manifests itself as muscle hypertonicity, trembling and difficulty in controlling movements. Currently, about 4 million people on the planet suffer from this disease, and by 2030 this number is expected to double.
It is known that hereditary forms of the disease are characterized by mutations in the parkin gene, and the protein encoded by this gene is involved in the degradation of some other proteins, but exactly how disorders in the protein encoded by the parkin gene are associated with the development of parkinsonism has not yet been clarified.
Scientists from the Montreal Neurological Institute and Mcgril University Hospital, working under the guidance of Professor Edward Fon, identified the most frequently mutating fragment of the parkin gene and studied the functions of the protein region encoded by this gene fragment using NMR, biochemical approaches and methods of structural biology and other approaches. When searching for proteins interacting with this domain, the researchers found endophilin-A protein that plays a major role in the process of synaptic transmission (the way nerve cells "communicate" with each other). The process of signal transmission between neurons consists in the release of a neurotransmitter from the synaptic vesicle from the surface of one neuron into the synaptic cleft, its movement to the surface of another nerve cell and the absorption of a neurotransmitter by this cell – a process called endocytosis, in which endophilin-A plays a leading role.
Scientists have found that mutations in the parkin gene associated with the hereditary form of Parkinson's disease lead to disruption of the synaptic neurotransmission process, probably due to a malfunction of the endocytosis system associated with the functioning of endophilin-A.
Currently, there are no drugs that act on the causes of Parkinson's disease and can cure people of it. There are only symptomatic drugs aimed at alleviating the condition of patients.
The identification of the link between Parkinson's disease, mutations in the parkin gene and endophilin-A-mediated disruption of the endocytosis system opens up new opportunities for the development of drugs aimed at restoring the interaction between the parkin gene product and endophilin-A and correcting a defect in the signal transmission system between nerve cells.
We hope that in the near future an effective medicine will be created that acts on the cause of this serious disease and, contrary to forecasts, in 20 years the number of patients with Parkinsonism will not double, but decrease.
The article by Jean-François Trempe et al., "SH3 Domains from a Subset of BAR Proteins Define a Ubl-Binding Domain and Implicate Parkin in Synaptic Ubiquitination" was published in the journal Molecular Cell at the end of last year and noted by the editor-in-chief of the journal Science.
Daria Chervyakova
Portal "Eternal youth" http://vechnayamolodost.ru Based on ScienceDaily: Communication Breakdown: What Happens to Nerve Cells in Parkinson's Disease.
15.02.2010