Spanish Scientists, coordinated by a group from the Idibaps-hospital Clínic of Barcelona, have identified for the first time, numerous changes in the epigenome of patients with párkinson.
the main novelty of The work, published by the scientific journal “EMBO Molecular Medicine”, is the discovery of epigenetic alterations in the párkinson, until now, been little explored, through the use of a system of dopaminergic neurons derived from patients with this disease at the hospital Clínic.
Parkinson’s disease is a multifactorial neurodegenerative disease whose mechanisms are poorly known because it is due in part to the dopaminergic neurons affected by the disease are found in a region deep brain named ‘substantia nigra’ which is only accessible post-mortem, after many years of illness of the patient, when the majority of these cells have already degenerated.
The work has been coordinated by Rubén Fernández-Santiago and Mario Ezquerra, from the group of Parkinson’s Idibaps, and is part of a collaborative project Ciberned directed by Eduardo Tolosa.
The study brings together interdisciplinary collaboration of experts in fields such as epigenetics (Ignacio Martín-Subero, Idibaps), regenerative medicine (Antonella Consiglio Institute of Biomedicine of the University of Barcelona and Angel Raya Institute for Bioengineering of Catalonia) and neuroscience (Miquel Vila, Vall d’’hebron Institut de Recerca, VHIR), among others.
In the study, the researchers isolated somatic cells obtained by biopsy from the skin of patients (fibroblasts) reprogrammed to induced pluripotent stem cells (iPSC), and differentiated into dopaminergic neurons.
then, analyzed the epigenome and the transcriptome of dopaminergic neurons and identified for the first time more than 2,000 epigenetic changes, and also gene expression distributed throughout the genome of the patients.
“These epigenetic alterations could be of great importance in Parkinson’s disease, since the epigenome is the set of molecular mechanisms that allow you to activate or deactivate the expression of the genome”, explained Fernández-Santiago.
The researchers found that the majority of epigenetic changes affect regions regulatory key called ‘enhancers’, and are related to the deficit of a network of transcription factors relevant to the párkinson.
Another breakthrough is that the study compares for the first time, the epigenome of patients with párkinson sporadic (90-95% of cases), and with familial pd-associated mutations in the LRRK2 gene, discovering that both forms share the same epigenetic alterations among themselves with respect to healthy people.
These results indicate that the sporadic forms and the familial forms of párkinson could share common mechanisms, at least from the point of view of epigenetic, which opens the door to possible treatments common in the future.
The work also describes the epigenetic alterations detected in the párkinson are not present on fibroblasts, stem cells, iPSC, or in other types of neurons and are manifest specifically only after the differentiation into dopaminergic neurons.
These results suggest that Parkinson’s disease may have a systemic character and affect globally to the agency, “that is to say, that the own fibroblasts could already have some type of molecular defect, due, in part, to the environmental history of the individual, and that would only be pathogenic in the dopaminergic neurons”, according to Ezquerra