A study carried out by researchers from the Neuromuscular Diseases laboratory of the Research Institute of the Hospital de la Santa Creu i Sant Pau – IIB Sant-Pau and the Memory Unit of the Neurology Service of the same hospital, which is directed by Dr. Alberto LLeó, has concluded that patients with amyotrophic lateral sclerosis (ALS) have abnormally high levels of NOD2 and Spp1 proteins, so these molecules are postulated as new biomarkers in the pathophysiology of this neurodegenerative disease.
The work, published by the journal Neurology Neuroimmunology and Neuroinflammation, provides data that contributes to a better understanding of the biological basis of this disease, according to Dr. Ricardo Rojas-García, researcher in the Neuromuscular Diseases group at IIB Sant Pau and one of the main authors of the study.
ALS is a neurodegenerative disease that affects nerve cells in the brain and spinal cord, causing rapidly progressive muscle weakness. Although its symptoms are well known and its clinical diagnosis is relatively simple, its origin is still a mystery and its pathophysiology is still poorly understood. So far, no specific biomarkers are known for molecular diagnosis or to predict the prognosis.
In virtually all patients with ALS, it can be seen that there is an anomalous deposit of proteins in the motor neurons of the cerebral cortex, motor nuclei of the brainstem and anterior horns of the spinal cord, that is to say, they are delocalized and deposited in inclusions in the cytoplasm of these neurons.
“Through neuropathological studies, what we see is that there is an abnormal deposit of proteins. In other words, some proteins that are normally physiologically found in the nucleus are deposited in the cytoplasm”, explains Dr. Rojas-Garcia.
NOD2 and Spp1 proteins are involved in the specific pathophysiological pathway of innate immunity and protein homeostasis, “which makes a lot of sense and leads us to think that they probably play a role in the mechanism by which proteins are deposited in the brain of patients with ALS”, explains the researcher.
One more step to know the pathophysiology of the disease.
The main objective of this study, which has been carried out in collaboration with the Navarra Research Institute (IdisNA), within the framework of the Center for Biomedical Research in the Rare Diseases Network (CIBERER) and the Center of Biomedical Research in the Network of Neurodegenerative Diseases (CIBERNED), was to try to find both diagnostic and prognostic biomarkers for ALS.
The researchers analyzed data from a cohort of 123 ALS patients, 30 Alzheimer’s disease patients, 28 frontotemporal dementia patients and 102 age-matched healthy controls. The results showed that NOD2 protein levels were significantly higher in ALS patients compared to participants diagnosed with Alzheimer’s, frontotemporal dementia and the control group. This is the first time that NOD2 has been associated with the pathophysiology of ALS.
In addition, the study found that Spp1 levels were elevated in ALS patients compared to healthy participants. However, no significant differences were found in the levels of this protein between patients with ALS and patients with Alzheimer’s or frontotemporal dementia.
“Our data support an important role of the neuroinflammation process in the pathophysiology of ALS and may be useful to help identify new targets for research and development of treatments that can modulate these pathways for these patients” , concludes Dr. Rojas-Garcia.
Reference article
Noemí de Luna, Álvaro Carbayo, Oriol Dols-Icardo, Janina Turon-Sans, David Reyes-Leiva, Ignacio Illan-Gala, Ivonne Jericó, Inma Pagola-Lorz, Cinta Lleixà, Luis Querol, Sara Rubio-Guerra, Daniel Alcolea, Juan Fortea, Alberto Lleó, Elena Cortés-Vicente, Ricardo Rojas-Garcia. Neuroinflammation-Related Proteins NOD2 and Spp1 Are Abnormally Upregulated in Amyotrophic Lateral Sclerosis. Neurol Neuroimmunol Neuroinflamm Mar 2023, 10 (2) e200072; DOI: 10.1212/NXI.0000000000200072
