Molecular Alterations in Sporadic and SOD1-ALS Immortalized Lymphocytes: Towards a Personalized Therapy
Abstract
:1. Introduction
2. Results
2.1. Oxidative Stress, Bioenergetic, and Metabolic Profiles of Lymphoblasts from Healthy Subjects, and Sporadic or SOD1 Mutation Carrier ALS Patients
2.2. Different Profile of NRF2-Pathway between Sporadic and SOD1 Mutation Carriers ALS Patient’s Lymphoblast
2.3. Sporadic and SOD1-Mutation Carriers ALS Patients Lymphoblast Showed Distinct Pro-Inflammatory Cytokines Profile
2.4. Different Autophagic Profile between Sporadic and SOD1 Mutation Carriers ALS Patient’s Lymphoblasts
3. Discussion
4. Materials and Methods
4.1. Materials
4.2. Lymphoblastic Cell Lines
4.3. Measurement of Reactive Oxygen Species (ROS) and Thiobarbituric Acid Reactive Substances (TBARs)
4.4. Oxygen Consumption and Extracellular Acidification Rates Measurements
4.5. HRMAS-NMR Acquisition and Processing
4.6. Analysis of mRNA Levels by Quantitative Real-Time PCR
4.7. Immunoblotting
4.8. Statistical Analyses
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Patient ID | Clinic Presentation | Affected Motoneurons | Age | Gender | Mutation |
---|---|---|---|---|---|
C-34 | n/a | 88 | Female | ---- | |
C-35 | n/a | 63 | Male | ---- | |
C-37 | n/a | 57 | Female | ---- | |
C39 | n/a | 53 | Female | ---- | |
C105 | n/a | 54 | Female | ---- | |
C106 | n/a | 67 | Female | ---- | |
C107 | n/a | 58 | Female | ---- | |
C108 | n/a | 68 | Female | ---- | |
C110 | n/a | 75 | Male | ---- | |
C112 | n/a | 71 | Male | ---- | |
C122 | n/a | 77 | Male | ---- | |
C123 | n/a | 55 | Male | ---- | |
C132 | n/a | 52 | Male | ---- | |
E2 | Bulbar | MNS | 76 | Female | * |
E4 | bulbar | MNS & MNI | 54 | Female | * |
E5 | Spinal | MNS | 54 | Female | * |
E6 | Bulbar | MNI | 79 | Male | * |
E8 | Respiratory | MNI | 55 | Male | * |
E10’ | Bulbar | MNS | 68 | Male | * |
E11 | Spinal | MNI | 64 | Male | SOD1 het N65S |
E18-5 | Spinal | MNI | 46 | Male | SOD1 het p.Leu117Val |
E18-6 | Spinal | MNS & MNI | 58 | Male | SOD1 het p.ASn139His |
E18-7 | Spinal | MNI | 59 | Male | SOD1 het p.Leu117Val |
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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, 22, 3007. https://doi.org/10.3390/ijms22063007
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. International Journal of Molecular Sciences. 2021; 22(6):3007. https://doi.org/10.3390/ijms22063007
Chicago/Turabian StyleLastres-Becker, Isabel, Gracia Porras, Marina Arribas-Blázquez, Inés Maestro, Daniel Borrego-Hernández, Patricia Boya, Sebastián Cerdán, Alberto García-Redondo, Ana Martínez, and Ángeles Martin-Requero. 2021. "Molecular Alterations in Sporadic and SOD1-ALS Immortalized Lymphocytes: Towards a Personalized Therapy" International Journal of Molecular Sciences 22, no. 6: 3007. https://doi.org/10.3390/ijms22063007