Scientists have solved a longstanding problem with modeling Parkinson\u2019s disease in animals. Using newfound insights, they improve both cell and animal models for the disease, which can propel research and drug development.<\/p>\n
Parkinson’s disease is characterized by the appearance of protein clumps within neurons in the brain, called Lewy bodies. Reproducing Lewy bodies in animals in order to model the disease for research and drug screening has proven notoriously difficult, leaving a gap in Parkinson\u2019s research and treatment. Scientists have now shown where the discrepancy between humans and animals lies. Using the knowledge, the scientists have produced cellular and mouse models that reproduce the evolution of Parkinson\u2019s disease more accurately for both fundamental research and drug development. The work is published in PNAS<\/em>.<\/p>\n In humans, Lewy bodies form when the brain produces twice the normal amount of alpha-synuclein. When mice, which are often used to model human diseases, are used to model Parkinson\u2019s, they are genetically engineered to overproduce it. But human alpha-synuclein does not form fibrils and Lewy bodies when produced in mice.<\/p>\n Mice produce three types of their own synuclein, which are similar to human alpha-synuclein. Because of this, they are referred to as its \u201chomologues\u201d. The researchers found that human alpha-synuclein does not form Lewy bodies in mice because its homologues in the animal prevent it from doing so. This discovery explains why it is so difficult to model Parkinson\u2019s disease in normal mice, which have all of their synuclein homologues. In other words, the key to successfully modeling the disease in mice is to genetically suppress their homologues of human alpha-synuclein.<\/p>\n