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The team lead by Antonella Consiglio, researcher at IBUB, the Faculty of Medicine and Health Sciences of UB, and IDIBELL (Photo: IDIBELL).
 14.01.2019

Defective glial cells can push neurons toward Parkinson’s disease

Defective versions of human brain cells called astrocytes are linked to the buildup of a toxic protein that is one the hallmarks of Parkinson's disease. This is one of the main conclusions of a study led by Antonella Consiglio, researcher at the Institute of Biomedicine of the University of Barcelona (IBUB) in the Barcelona Science Park, and the Bellvitge Biomedical Research Institute (IDIBELL), and Àngel Raya, from the Center of Regenerative Medicine in Barcelona (CMR[B]-IDIBELL).

 

Star-shaped astrocytes extend branching tendrils around synapses and along blood vessels. It was known by post-mortem analysis of brain tissue from Parkinson’s disease patients that astrocytes showed abnormal accumulation of α-synuclein. However, this was interpreted by most researchers as a secondary response, as if astrocytes were trying to clear up α-synuclein aggregates from neurons.

In view of these previous studies, the researchers decided to develop a new cell culture system from human cells. Using cells derived from Parkinson’s patients with a LRRK2 mutation, in collaboration with Dr. E. Tolosa from the Unit of Movement Disorders at Hospital Clínic, in Barcelona, the researchers generated stem-cell-derived glia cells.

The astrocytes studied in this work, derived from Parkinson’s disease patients with a genetic mutation that affects cell clean-up functions, caused more accumulation of the toxin, α -synuclein, than those derived from healthy individuals. The work, which appears January 10 in the journal Stem Cell Reports, suggests an important role for glial cells in Parkinson’s disease and offers potential new targets for developing therapies.

“Our overall results completely turn our previous view of the participation of astrocytes in Parkinson’s disease upside down. From mainly bystander cells with some early protective role, we believe they should now be considered as critical players that spread the disease and amplify the degree of neuronal degeneration,” says Antonella Consiglio, researcher at IBUB, IDIBEL, and the Faculty of Medicine and Health Sciences of the University of Barcelona.

Other researchers from the Barcelona Science Park on the paper are Juan Pablo Muñoz, Antonio Zorzano at the Institute for Research in Biomedicine (IRB Barcelona), and Marta Gut at Centre Nacional d’Anàlisi Genòmica (CNAG-CRG).

Journal Reference: Angelique di Domenico, Giulia Carola, Carles Calatayud, Meritxell Pons-Espinal, Juan Pablo Muñoz, Yvonne Richaud-Patin, Irene Fernandez-Carasa, Marta Gut, Armida Faella, Janani Parameswaran, Jordi Soriano, Isidro Ferrer, Eduardo Tolosa, Antonio Zorzano, Ana Maria Cuervo, Angel Raya, Antonella Consiglio. “Patient-Specific iPSC-Derived Astrocytes Contribute to Non-Cell-Autonomous Neurodegeneration in Parkinson’s Disease“. Stem Cell Reports, 2019; DOI: 10.1016/j.stemcr.2018.12.011

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