Research Paper|Volume 12, Issue 17|pp 16690—16708

Metabolic alterations in plasma from patients with familial and idiopathic Parkinson’s disease

Sokhna M.S. Yakhine-Diop^1,^2,³, José A. Morales-García^2,^4,⁵, Mireia Niso-Santano^1,^2,³, Rosa A. González-Polo^1,^2,³, Elisabet Uribe-Carretero^1,^2,³, Guadalupe Martinez-Chacon^1,^2,³, Sylvere Durand⁶, Maria Chiara Maiuri^6,⁷, Ana Aiastui^2,^8,⁹, Miren Zulaica^2,⁹, Javier Ruíz-Martínez^2,^9,^10,¹¹, Adolfo López de Munain^2,^9,^10,^11,¹², Jordi Pérez-Tur^2,^13,¹⁴, Ana Pérez-Castillo^2,⁴, Guido Kroemer^6,^7,^15,^16,¹⁷, José M. Bravo-San Pedro^2,¹⁸, José M. Fuentes^1,^2,³

¹Departamento de Bioquímica y Biología Molecular y Genética. Facultad de Enfermería y Terapia Ocupacional. Universidad de Extremadura, Cáceres, Spain
²Centro de Investigación Biomédica en Red en Enfermedades Neurodegenerativas (CIBERNED), Madrid, Spain
³Instituto Universitario de Investigación Biosanitaria de Extremadura (INUBE), Cáceres, Spain
⁴Instituto de Investigaciones Biomédicas (CSIC-UAM) “Alberto Sols” (CSIC-UAM), Madrid, Spain
⁵Departamento de Biología Celular, Facultad de Medicina, Universidad Complutense de Madrid, Madrid, Spain
⁶Metabolomics and Cell Biology Platforms, Institut Gustave Roussy, Villejuif, France
⁷Centre de Recherche des Cordeliers, Equipe labellisée par la Ligue contre le cancer, Inserm U1138, Université de Paris, Sorbonne Université, Paris, France
⁸Cell Culture Platform, Biodonostia Health Research Institute, San Sebastián, Spain
⁹Neuroscience Area of Biodonostia Health Research Institute, Donostia University Hospital, San Sebastián, Spain
¹⁰, Donostia University Hospital, Department of Neurology, OSAKIDETZA, Spain
¹¹Ilundain Foundation, San Sebastian, Spain
¹²Department of Neurosciences, University of the Basque Country UPV-EHU, San Sebastián, Spain
¹³Instituto de Biomedicina de Valencia-CSIC, Unidad de Genética Molecular, Valencia, Spain
¹⁴Unidad Mixta de Genética y Neurología, Instituto de Investigación Sanitaria La Fe, Valencia, Spain
¹⁵, Pôle de Biologie, Hôpital Européen Georges Pompidou, AP-HP, France
¹⁶Suzhou Institute for Systems Medicine, Chinese Academy of Medical Sciences, Suzhou, China
¹⁷Karolinska Institute, Department of Women's and Children's Health, Karolinska University Hospital, Stockholm, Sweden
¹⁸Departamento de Fisiología, Facultad de Medicina, Universidad Complutense de Madrid, Madrid, Spain

* Co-Senior authors

Received: June 17, 2020Accepted: August 15, 2020Published: September 9, 2020

https://doi.org/10.18632/aging.103992

Copyright: © 2020 Yakhine-Diop et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

The research of new biomarkers for Parkinson’s disease is essential for accurate and precocious diagnosis, as well as for the discovery of new potential disease mechanisms and drug targets. The main objective of this work was to identify metabolic changes that might serve as biomarkers for the diagnosis of this neurodegenerative disorder. For this, we profiled the plasma metabolome from mice with neurotoxin-induced Parkinson’s disease as well as from patients with familial or sporadic Parkinson’s disease. By using mass spectrometry technology, we analyzed the complete metabolome from healthy volunteers compared to patients with idiopathic or familial (carrying the G2019S or R1441G mutations in the LRRK2 gene) Parkinson’s disease, as well as, from mice treated with 6-hydroxydopamine to induce Parkinson disease. Both human and murine Parkinson was accompanied by an increase in plasma levels of unconjugated bile acids (cholic acid, deoxycholic acid and lithocholic acid) and purine base intermediary metabolites, in particular hypoxanthine. The comprehensive metabolomic analysis of plasma from Parkinsonian patients underscores the importance of bile acids and purine metabolism in the pathophysiology of this disease. Therefore, plasma measurements of certain metabolites related to these pathways might contribute to the diagnosis of Parkinson’s Disease.