The role of lipids, key in the development of amyotrophic lateral sclerosis

People suffering from amyotrophic lateral sclerosis (ALS) have an altered composition of fats in their spinal cord cells. This has been confirmed by a pilot study conducted by researchers at the Institute for Research in Biomedicine of Lleida (IRBLleida) and the University of Lleida (UdL) and the Catalan Institute of Health Lleida to analyse the nuclear lipidome (the envelope of the cell site where genetic information is stored). The results, published in the Journal of Neurochemistry, support the usefulness of lipidomics applied to neurodegenerative diseases and the ageing process.

The study - led by Omar Ramírez-Núñez, Mariona Jové, Pascual Torres and Reinald Pamplona from the Metabolic Physiopathology group at IRBLleida and the Department of Experimental Medicine at the University of Lleida - has had the collaboration of the Catalan Institute of Health, the University Institute for Primary Health Care Research Foundation Jordi Gol and Gurina (IDIAPJGol-Primary Care Lleida), the Bellvitge University Hospital, the Bellvitge Biomedical Research Institute (IDIBELL), the University of Barcelona and the Institute of Neurosciences of the UB (UBNEuro) and CIBERNED (Centre for Biomedical Research Network on Neurodegenerative Diseases).

The pilot study has worked with samples from around thirty patients from the Arnau de Vilanova University Hospital (HUAV), the University Hospital of Santa Maria (HUSM) and the Hospital de Bellvitge. "We have seen how the production of a special type of fat, called ether-lipids, could be altered in ALS patients," explains the researcher in charge and professor at the University of Lleida, Manel Portero. "We have observed a decrease in their concentration. We don't know if by solving this problem we can help patients, but it is a new potential avenue of action to discover new targets for developing possible drugs," he adds.

ALS is a neurodegenerative disease characterised by progressive loss of movement, as it affects motor neurons in the brain, brainstem and spinal cord, which are the cells responsible for transmitting the order for voluntary movement from the brain to the muscles. The causes of this minority disease are unknown. "We have shown that within ALS-affected tissues there are changes in lipids that could be related to the speed of the disease or even its cause. We need to continue researching," says Portero.

Lipidomics is dedicated to the study and characterisation of lipids (fats), molecules that store energy in the body, form the cell envelopes and play an important role in cell signalling. The lipidome or lipid profile of a cell indicates the composition and abundance of lipids in our organism. IRBLleida and the University of Lleida have a scientific-technical lipidomics service, which has developed and consolidated the Lipidomics Platform of Catalonia (PLICAT).

The research has been made possible thanks to the research grants received by the research staff: grant 278486 Seventh Framework Programme of the European Commission of the European Union, grant 2017SGR696 from the Agència de Gestió d'Ajuts Universitaris i de Recerca de la Generalitat de Catalunya, grants PI14/1115, 14/003218 and PI17-00134 from the Instituto de Salud Carlos III, aid RTI2018-099200-B-I00 from the Ministry of Science and Innovation, aid PP00111 from the Fundació la Marató de TV3, aid Marie Curie Cofund IRBLleida-IPP, aid FPU16/01446 from the Ministry of Education, aid FUNDELA, RedELA-Plataforma Investigación and aid from the Fundació Miquel Valls.

Following in the same line of research, a study published in the journal Brain Communications, led by Professor Manuel Portero-Otín, and with the research staff, Joaquim Sol, Mariona Jové and Victòria Ayala, from the UdL, the Catalan Institute of Health, the IRBLleida and the IDIAPJGol, and other researchers from the Hospital de Bellvitge, IDIBELL, the University of Oxford, King's College London, the University of Barcelona and Columbia University, shows that the lipidomic characteristics of plasma and cerebrospinal fluid of people with ALS correlate with the progression of the disease.

"There are some lipids that, the higher their concentration in the cerebrospinal fluid, the faster the disease progresses," explains Manel Portero. This finding will make it possible to use lipid profiles as classifiers of ALS. In this case, the research has also been possible thanks to the research grants received by the research staff, in addition to the ERDF co-funding "A way tone build Europe" from the European Union.

Article:

Ramírez-Nuñez O, Jové M, Torres P, Sol J, Fontdevila L, Romero-Guevara R, Andrés-Benito P, Ayala V, Rossi C, Boada J, Povedano M, Ferrer I, Pamplona R, Portero-Otin M. Nuclear lipidome is altered in amyotrophic lateral sclerosis: A pilot study. J Neurochem. 2021 Apr 27. doi: 10.1111/jnc.15373. Epub ahead of print. PMID: 33905537.

Article:
Sol J, Jové M, Povedano M, Sproviero W, Domínguez R, Piñol-Ripoll G, Romero-Guevara R, Hye A, Al-Chalabi A, Torres P, Andres-Benito P, Area-Gómez E, Pamplona R, Ferrer I, Ayala V, Portero-Otin M. Lipidomic traits of plasma and cerebrospinal fluid in ALS correlate with disease progression. 2021 Apr 27.