麻豆传媒

Now, a new laboratory model of Parkinson鈥檚 is giving scientists an inside look at what happens in the brain years before motor symptoms appear. Specifically, it demonstrates how abnormal alpha-synuclein proteins, which are strongly associated with Parkinson鈥檚, gradually spread from an area of the brain implicated in the early stages of the disease to other regions of the brain ultimately damaged by the disease. The findings were .

Parkinson鈥檚 is primarily a disease of aging, with most cases diagnosed after age 60. By the time symptoms appear, more than half of the brain cells that produce dopamine, a chemical messenger needed for voluntary movement, have died. What triggers this process is unknown, although evidence points to a combination of genetic, epigenetic and environmental factors. Strong evidence also suggests that clumps of abnormal alpha-synuclein play a role in the disease process. In recent years, scientists have found links to the early stages of Parkinson鈥檚 in other areas of the body, namely the gut and the nose.

鈥淏etter models that mimic the early stages of the disease will allow us to more precisely study Parkinson鈥檚 and, by extension, find new ways to potentially stop it before it progresses,鈥� said Van Andel Research Institute researcher , the study鈥檚 first author. 鈥淲e know that specific signs of Parkinson鈥檚, including a loss of sense of smell, appear years before the onset of motor symptoms. Our new model replicates the phase that occurs long before diagnosis and, importantly, gives us a powerful tool to test novel interventions that might prevent the onset of Parkinson鈥檚 as we know it.鈥�

The study demonstrates that alpha-synuclein travels along nerve cells in the olfactory bulb鈥攖he part of the brain that controls sense of smell鈥攑rior to the onset of motor symptoms and that this area may be particularly susceptible to the spread of alpha-synuclein, ultimately causing deficits in the sense of smell. Clumps of alpha-synuclein eventually reach several additional brain regions, including the brainstem area that houses dopamine cells.

鈥淧erhaps most remarkably, we have created a model of prodromal Parkinson鈥檚 disease, the condition that precedes the diagnosis of the disorder in humans by five to 10 years, that successfully mimics the pattern of alpha-synuclein鈥檚 pathology in the brain,鈥� said , senior author of the study and director of Van Andel Research Institute鈥檚 Center for Neurodegenerative Science. 鈥淣ot only might this teach us something about how the disease develops and the importance of the olfactory system, but the model will also prove invaluable when testing novel therapeutics designed to slow down or stop the progression of disease.鈥�

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This work was supported by Van Andel Research Institute, the Peter C. and Emajean Cook Foundation, the European Research Council and University of Pennsylvania Morris K. Udall Parkinson鈥檚 Disease Research Center of Excellence. Other study authors include Jennifer A. Steiner (Van Andel Research Institute), Nazia Maroof (Roche Innovation Center), Kelvin C. Luk (University of Pennsylvania), Zachary Madaj (Van Andel Research Institute), John Q. Trojanowski (University of Pennsylvania), and Virginia M-Y Lee (University of Pennsylvania).

Rey NL, Steiner JA, Maroof N, Luk KC, Madaj Z, Trojanowski JQ, Lee VMY, Brundin P. In press. . J Exp Med.

ABOUT VAN ANDEL RESEARCH INSTITUTEVan Andel Institute (VAI) is an independent nonprofit biomedical research and science education organization committed to improving the health and enhancing the lives of current and future generations. Established by Jay and Betty Van Andel in 1996 in Grand Rapids, Michigan, VAI has grown into a premier research and educational institution that supports the work of more than 360 scientists, educators and staff. , VAI鈥檚 research division, is dedicated to determining the epigenetic, genetic, molecular and cellular origins of cancer, Parkinson鈥檚 and other diseases and translating those findings into effective therapies. The Institute鈥檚 scientists work in onsite laboratories and participate in collaborative partnerships that span the globe. 100% To Research, Discovery & Hope庐