000126529 001__ 126529
000126529 005__ 20241125101140.0
000126529 0247_ $$2doi$$a10.3390/jcm12103560
000126529 0248_ $$2sideral$$a134004
000126529 037__ $$aART-2023-134004
000126529 041__ $$aeng
000126529 100__ $$aGonzález-Mingot, Cristina
000126529 245__ $$aMitochondrial aconitase enzymatic activity: a potential long-term survival biomarker in the blood of ALS patients
000126529 260__ $$c2023
000126529 5060_ $$aAccess copy available to the general public$$fUnrestricted
000126529 5203_ $$aBackground: 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.
000126529 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000126529 590__ $$a3.0$$b2023
000126529 592__ $$a0.882$$b2023
000126529 591__ $$aMEDICINE, GENERAL & INTERNAL$$b59 / 329 = 0.179$$c2023$$dQ1$$eT1
000126529 593__ $$aMedicine (miscellaneous)$$c2023$$dQ1
000126529 594__ $$a5.7$$b2023
000126529 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000126529 700__ $$0(orcid)0000-0001-5981-5448$$aMiana-Mena, Francisco Javier$$uUniversidad de Zaragoza
000126529 700__ $$0(orcid)0000-0002-8751-7779$$aIñarrea, Pedro José$$uUniversidad de Zaragoza
000126529 700__ $$aIñiguez, Cristina
000126529 700__ $$aCapablo, José Luis
000126529 700__ $$0(orcid)0000-0001-5687-6704$$aOsta, Rosario$$uUniversidad de Zaragoza
000126529 700__ $$aGil-Sánchez, Anna
000126529 700__ $$aBrieva, Luis
000126529 700__ $$aLarrodé, Pilar
000126529 7102_ $$11001$$2420$$aUniversidad de Zaragoza$$bDpto. Anatom.,Embri.Genét.Ani.$$cÁrea Genética
000126529 7102_ $$11012$$2410$$aUniversidad de Zaragoza$$bDpto. Farmac.Fisiol.y Med.L.F.$$cÁrea Fisiología
000126529 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000126529 773__ $$g12, 10 (2023), 3560 [12pp.]$$pJ. clin.med.$$tJournal of Clinical Medicine$$x2077-0383
000126529 8564_ $$s1333918$$uhttps://zaguan.unizar.es/record/126529/files/texto_completo.pdf$$yVersión publicada
000126529 8564_ $$s2860326$$uhttps://zaguan.unizar.es/record/126529/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000126529 909CO $$ooai:zaguan.unizar.es:126529$$particulos$$pdriver
000126529 951__ $$a2024-11-22-12:02:14
000126529 980__ $$aARTICLE