Mitochondrial aconitase enzymatic activity: a potential long-term survival biomarker in the blood of ALS patients
Resumen: Background: Amyotrophic lateral sclerosis (ALS) is a multisystemic, progressive, neurodegenerative disorder. Despite it being generally fatal within a period of 2–4 years, it is highly heterogeneous; as a result, survival periods may vary greatly among individual patients. Biomarkers can serve as tools for diagnosis, prognosis, indicators of therapeutic response, and future therapeutics. Free-radical-dependent mitochondrial damage is believed to play a crucial role in neurodegeneration in ALS. Mitochondrial aconitase, which is also known as aconitase 2 (Aco2), is a key Krebs cycle enzyme and is involved in the regulation of cellular metabolism and iron homeostasis. Aco2 is very sensitive to oxidative inactivation and can aggregate and accumulate in the mitochondrial matrix, causing mitochondrial dysfunction. Loss of Aco2 activity may therefore reflect increased levels of mitochondrial dysfunction due to oxidative damage and could be relevant to ALS pathogenesis. The aim of our study was to confirm changes in mitochondrial aconitase activity in peripheral blood and to determine whether such changes are dependent on, or independent of, the patient’s condition and to propose the feasibility of using them as possible valid biomarkers to quantify the progression of the disease and as a predictor of individual prognosis in ALS. Methods: We measured the Aco2 enzymatic activity in the platelets of blood samples taken from 22 controls and 26 ALS patients at different stages of disease development. We then correlated antioxidant activity with clinical and prognostic variables. Results: Aco2 activity was significantly lower in the 26 ALS patients than in the 22 controls (p < 0.05). Patients with higher levels of Aco2 activity survived longer than those with lower levels (p < 0.05). Aco2 activity was also higher in patients with earlier onset (p < 0.05) and in those with predominantly upper motor neuron signs. Conclusions: Aco2 activity seems to be an independent factor that could be used in the long-term survival prognosis of ALS. Our findings suggest that blood Aco2 could be a leading candidate for use as a biomarker to improve prognosis. More studies are needed to confirm these results.
Idioma: Inglés
DOI: 10.3390/jcm12103560
Año: 2023
Publicado en: Journal of Clinical Medicine 12, 10 (2023), 3560 [12pp.]
ISSN: 2077-0383

Tipo y forma: Article (Published version)
Área (Departamento): Área Genética (Dpto. Anatom.,Embri.Genét.Ani.)
Área (Departamento): Área Fisiología (Dpto. Farmac.Fisiol.y Med.L.F.)
Área (Departamento): Área Bioquímica y Biolog.Mole. (Dpto. Bioq.Biolog.Mol. Celular)

Creative Commons You must give appropriate credit, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use.

Exportado de SIDERAL (2023-10-06-14:13:50)

Este artículo se encuentra en las siguientes colecciones:

 Record created 2023-07-06, last modified 2023-10-06

Versión publicada:
Rate this document:

Rate this document:
(Not yet reviewed)