Nature: does Parkinson's disease begin before birth? New model tests preventive drugs

According to new research by cedars Sinai, people with Parkinson's disease before the age of 50 may be born with dysfunctional brain cells, which have not been discovered for decades, and a drug that may help to correct the process of these diseases Dr Clive Svendsen, director of cedars Sinai Institute of regenerative medicine, and Dr Nur yucer, project scientist, discussed the microscopic images of dopamine neurons Photo source: cedars Sinai When the neurons in the brain that make dopamine are damaged or die, it can lead to Parkinson's disease Over time, the symptoms will become more and more serious, including tardiness, muscle rigidity, shaking and imbalance Although the majority of patients were 60 years old or older at the time of diagnosis, about 10% were between 21 and 50 years old The new study, published in the journal Nature Medicine, focuses on these young patients https://doi.org/10.1038/s41591-019-0739-1 To carry out the study, the team produced special stem cells called induced pluripotent stem cells (iPSCs) from cells from patients with early-onset Parkinson's disease (YOPD) This process allows adult blood cells to "rewind time" back to the primordial embryo state These iPSCs can produce any type of human cell, and are genetically identical to the patient's own cells The team used IPSC to produce dopamine neurons from each patient, then cultured them in a dish and analyzed the function of the neurons The researchers found two key abnormalities in dopamine neurons in the culture dish: the accumulation of a-synuclein, a protein found in most Parkinson's diseases; and the lysosomal dysfunction, which may lead to the accumulation of a-synuclein Using the new model, the researchers saw the first signs of early Parkinson's disease, in which dopamine neurons in these individuals may continue to misprocess alpha synuclein for 20 or 30 years, leading to Parkinson's symptoms The degradation of lysosomal α - synuclein is particularly impaired in YOPD midbrain dopaminergic (MDA) cultures The researchers also used IPSC models to test many drugs that might reverse the abnormality They found that pep005, an FDA approved drug for the treatment of precancerous skin lesions, reduced levels of alpha synuclein in dopaminergic neurons in Petri dishes and mice The drug also inhibited another abnormality they found in patients' dopamine neurons - an elevated level of an active enzyme called protein kinase C, although its role in Parkinson's disease is unclear Confirm the function and mechanism of pep005 Next, the research group plans to study how to deliver PEP005 currently available in gel form to the brain to potentially treat or prevent Parkinson's disease The team also plans to conduct more research to determine whether abnormalities found in neurons of patients with early-onset Parkinson's disease also exist in other forms of Parkinson's disease The technology provides researchers with a window of time to see how dopamine neurons function at the beginning of a patient's life, helping to identify high-risk groups early and take early action to prevent the disease.