Protein conveyed along neural pathways in disease models
Grand Rapids, Mich. (Aug. 13, 2013) – An international study demonstrates for the first time that a protein, misfolded in Parkinson’s disease patients, spreads from parts of the brain connected to the nose to other brain regions affected by the disease.
Parkinson´s disease is the second most common degenerative disorder of the central nervous system and one that currently strikes more than 1% of people over the age of 65. The causes of the disease and its development are not yet fully understood.
Researchers from Lund University, Lund, Sweden, Laboratoire d’Enzymologie et de Biochimie Structurale, CNRS, Gif-sur-Yvette, France, and Van Andel Institute, Grand Rapids, Mich., focused their efforts on the olfactory bulb, a structure of the brain involved in the perception of odors that is involved early in the disease. They based their research strategy on the hypothesis that the spread of a misfolded protein known as α-synuclein, which forms large aggregates in the brain of patients, is a crucial component of the development of the disease.
The study, “Transfer of human α-synuclein from the olfactory bulb to interconnected brain regions in mice,” published this week in the journal Acta Neuropathologica, demonstrates for the first time that α-synuclein injected into the olfactory bulb is taken up by neurons and transferred to interconnected regions of the brain in mice, and that the form of α-synuclein dramatically affects the process.
“The transfer to interconnected regions supports the idea that α-synuclein can transfer effectively along neural pathways and thereby can contribute to the progression of the α-synuclein-related pathology,” said Nolwen L. Rey, Ph.D., Postdoctoral Fellow, Neuronal Survival Unit, Lund University, Sweden and first author of the study. “After transfer, in young healthy mice, the injected proteins were gradually removed by the nerve cells. But we believe that when cellular mechanisms that protect against misfolded proteins fail, the misfolded α-synuclein could stay and trigger the formation of large protein aggregates that eventually impair or kill the cells.” Dr. Rey joins the staff of Van Andel Institute in early 2014.
Scientists conducted several experiments injecting different molecular species (of varying sizes and shapes) of human α-synuclein into the olfactory bulbs of mice. They found that the protein is taken up very quickly by neurons in the olfactory bulb. Then, within minutes to hours, the injected protein is also found in neurons in structures connected to the olfactory bulb. This ability to undergo rapid transport between brain regions seems to be a characteristic feature of the α-synuclein protein.
These new data are particularly important in the context of previous research work suggesting that, in people who are destined to eventually develop Parkinson’s disease, the large aggregates composed mainly of the α-synuclein protein develop and appear progressively in different brain regions. This spreading seems to follow a stereotypic pattern affecting certain brain regions such as the nose and the gut early in the disease and others later. A poor sense of smell is among the very first symptoms appearing in Parkinson’s disease, often several years before the patients experience problems with movement, supporting the importance of investigating olfaction and related brain structures in this disease.
“Parkinson’s is the second most common neurodegenerative disorder after Alzheimer’s disease,” said Patrik Brundin M.D., Ph.D., Jay Van Andel Endowed Chair in Parkinson’s Research at Van Andel Research Institute (VARI), Head of the Neuronal Survival Unit at Lund University and senior author of the study. “A major unmet medical need is a therapy that slows disease progression. We hope an understanding of how α-synuclein moves between brain regions will help uncover molecules that we can target with new drugs to slow the progression of symptoms in patients.”
About Van Andel Institute
Established by Jay and Betty Van Andel in 1996, Van Andel Institute (VAI) is an independent research and educational organization based in Grand Rapids, Mich., dedicated to preserving, enhancing and expanding the frontiers of medical science, and to achieving excellence in education by probing fundamental issues of education and the learning process. Van Andel Research Institute (VARI), VAI’s research arm, is dedicated to studying the genetic, cellular and molecular origins of cancer, Parkinson’s and other diseases and working to translate those findings into effective therapies. This is accomplished through the work of more than 200 researchers in on-site laboratories and in collaborative partnerships that span the globe. Find out more about Van Andel Institute or donate by visiting www.vai.org