| Yazarlar (7) |
Mukesh Gautam
Northwestern University Feinberg School Of Medicine, Amerika Birleşik Devletleri |
|
Ali Laith
Northwestern University Feinberg School Of Medicine, Amerika Birleşik Devletleri |
Prof. Dr. Aslıhan GÜNEL
Kırşehir Ahi Evran Üniversitesi, Türkiye |
|
Melda Yilmaz
Kocaeli Üniversitesi, Türkiye |
|
Nazli Basak
Koç Üniversitesi, Türkiye |
|
Halil Idrisoglu
İstanbul Tıp Fakültesi, Türkiye |
|
P. Hande Ozdinler
Northwestern University Feinberg School Of Medicine, Amerika Birleşik Devletleri |
| Özet |
| Amyotrophic lateral sclerosis (ALS) is a neuromuscular disease. Super oxide dismutase 1 (SOD1) gene mutations cause ALS, and the D90A mutation is associated with primarily upper motor neuron (UMN) loss. Objective: Our goal is to reveal the early cellular events in ALS pathology and identify potential pharmacokinetic biomarkers, using well-defined patient populations. Methods: Exosomes are isolated from serum either single or multiple time points from members of one family, who have SOD1D90A mutation, and their protein content is assessed by tandem mass-spec proteomics. Ingenuity Pathway analysis is used to highlight cellular events that are perturbed as the disease progressed. The linear regression analysis, using ALSFRS scores of patients and the protein content, helps identify potential pharmacokinetic biomarkers, which are confirmed with the ELISA assay. Results: Father, Son, and Daughter are at different disease stages and carry the SOD1D90A mutation. Albeit, the Daughter remained asymptomatic within a year; she had significant biological changes. The Son transitioned from asymptomatic to early symptomatic within a year, while the Father was symptomatic. Patient #2, who also had the SOD1D90A mutation, was more advanced. Comparison of the Son, Father, and Patient #2 suggested Fibronectin1 (FN1) as a potential pharmacokinetic biomarker, which is confirmed by ELISA. Interpretation: Exosome proteomics offer a powerful approach to interrogate disease-specific or disease-related proteins that become present in the blood. This helps define the perturbed cellular events with respect to disease progression and reveal potential pharmacokinetic biomarkers. We find FN1 levels to increase with disease progression, suggesting it may be a pharmacokinetic biomarker, especially for ALS patients with prominent UMN loss. |
| Anahtar Kelimeler |
| ALS | biomarker | exosomes | proteomics | SOD1 |
| Makale Türü | Özgün Makale |
| Makale Alt Türü | SSCI, AHCI, SCI, SCI-Exp dergilerinde yayınlanan tam makale |
| Dergi Adı | Annals of Clinical and Translational Neurology |
| Dergi ISSN | 2328-9503 Wos Dergi Scopus Dergi |
| Dergi Grubu | Q1 |
| Makale Dili | İngilizce |
| Basım Tarihi | 01-2025 |
| Sayı | 1 |
| Doi Numarası | 10.1002/acn3.70208 |
| Atıf Sayıları |
