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Title: Parkinson’s disease patient-specific neuronal networks carrying the LRRK2 G2019S mutation unveil early functional alterations that predate neurodegeneration
Author: Carola, Giulia
Malagarriga, Daniel
Calatayud Aristoy, Carles
Pons-Espinal, Meritxell
Blasco Agell, Lucas
Richaud-Patin, Yvonne
Fernandez-Carasa, Irene
Baruffi, Valentina
Beltramone, Silvia
Molina, Elsa
Dell’Era, Patrizia
Toledo Aral, Juan J.
Tolosa, Eduardo
Muotri, Alysson R.
Garcia Ojalvo, Jordi
Soriano i Fradera, Jordi
Raya Chamorro, Ángel
Consiglio, Antonella
Keywords: Malaltia de Parkinson
Mutació (Biologia)
Enginyeria genètica
Parkinson's disease
Mutation (Biology)
Genetic engineering
Issue Date: 2-Jul-2021
Publisher: Springer
Abstract: A deeper understanding of early disease mechanisms occurring in Parkinson's disease (PD) is needed to reveal restorative targets. Here we report that human induced pluripotent stem cell (iPSC)-derived dopaminergic neurons (DAn) obtained from healthy individuals or patients harboring LRRK2 PD-causing mutation can create highly complex networks with evident signs of functional maturation over time. Compared to control neuronal networks, LRRK2 PD patients' networks displayed an elevated bursting behavior, in the absence of neurodegeneration. By combining functional calcium imaging, biophysical modeling, and DAn-lineage tracing, we found a decrease in DAn neurite density that triggered overall functional alterations in PD neuronal networks. Our data implicate early dysfunction as a prime focus that may contribute to the initiation of downstream degenerative pathways preceding DAn loss in PD, highlighting a potential window of opportunity for pre-symptomatic assessment of chronic degenerative diseases.
Note: Reproducció del document publicat a:
It is part of: npj Parkinson's Disease, 2021, vol. 7, num. 55
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ISSN: 2373-8057
Appears in Collections:Articles publicats en revistes (Institut de Recerca en Sistemes Complexos (UBICS))
Articles publicats en revistes (Física de la Matèria Condensada)
Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)
Articles publicats en revistes (Patologia i Terapèutica Experimental)
Articles publicats en revistes (Institut de Biomedicina (IBUB))

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