RT Journal Article
T1 Molecular Alterations in Sporadic and SOD1-ALS Immortalized Lymphocytes: Towards a Personalized Therapy
A1 Lastres-Becker, Isabel
A1 Porras, Gracia
A1 Arribas Blázquez, Marina
A1 Maestro, Inés
A1 Borrego-Hernán, Daniel
A1 Boya, Patricia
A1 Cerdán, Sebastián
A1 García Redondo, Alberto
A1 Martínez, Ana
A1 Martin-Requero, Ángeles
AB Amyotrophic lateral sclerosis (ALS) is a fatal neurological condition where motor neurons (MNs) degenerate. Most of the ALS cases are sporadic (sALS), whereas 10% are hereditarily transmitted (fALS), among which mutations are found in the gene that codes for the enzyme superoxide dismutase 1 (SOD1). A central question in ALS field is whether causative mutations display selective alterations not found in sALS patients, or they converge on shared molecular pathways. To identify specific and common mechanisms for designing appropriate therapeutic interventions, we focused on the SOD1-mutated (SOD1-ALS) versus sALS patients. Since ALS pathology involves different cell types other than MNs, we generated lymphoblastoid cell lines (LCLs) from sALS and SOD1-ALS patients and healthy donors and investigated whether they show changes in oxidative stress, mitochondrial dysfunction, metabolic disturbances, the antioxidant NRF2 pathway, inflammatory profile, and autophagic flux. Both oxidative phosphorylation and glycolysis appear to be upregulated in lymphoblasts from sALS and SOD1-ALS. Our results indicate significant differences in NRF2/ARE pathway between sALS and SOD1-ALS lymphoblasts. Furthermore, levels of inflammatory cytokines and autophagic flux discriminate between sALS and SOD1-ALS lymphoblasts. Overall, different molecular mechanisms are involved in sALS and SOD1-ALS patients and thus, personalized medicine should be developed for each case.
SN 1422-0067
YR 2021
FD 2021
LK https://hdl.handle.net/20.500.14352/95536
UL https://hdl.handle.net/20.500.14352/95536
LA eng
NO Lastres-Becker I, Porras G, Arribas-Blázquez M, Maestro I, Borrego-Hernández D, Boya P, Cerdán S, García-Redondo A, Martínez A, Martin-Requero Á. Molecular Alterations in Sporadic and SOD1-ALS Immortalized Lymphocytes: Towards a Personalized Therapy. Int J Mol Sci. 2021 Mar 16;22(6):3007. doi: 10.3390/ijms22063007. PMID: 33809456; PMCID: PMC8000750.
DS Docta Complutense
RD 7 abr 2025