PMID- 35327493 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20220329 IS - 2227-9059 (Print) IS - 2227-9059 (Electronic) IS - 2227-9059 (Linking) VI - 10 IP - 3 DP - 2022 Mar 17 TI - The Potential Role of Peripheral Oxidative Stress on the Neurovascular Unit in Amyotrophic Lateral Sclerosis Pathogenesis: A Preliminary Report from Human and In Vitro Evaluations. LID - 10.3390/biomedicines10030691 [doi] LID - 691 AB - Oxidative stress, the alteration of mitochondrial function, and changes in the neurovascular unit (NVU) could play a role in Amyotrophic Lateral Sclerosis (ALS) pathogenesis. Our aim was to analyze the plasma redox system and nitric oxide (NO) in 25 ALS new-diagnosed patients and five healthy controls and the effects of plasma on the peroxidation/mitochondrial function in human umbilical cord-derived endothelial vascular cells (HUVEC) and astrocytes. In plasma, thiobarbituric acid reactive substances (TBARS), glutathione (GSH), and nitric oxide (NO) were analyzed by using specific assays. In HUVEC/astrocytes, the effects of plasma on the release of mitochondrial reactive oxygen species (mitoROS) and NO, viability, and mitochondrial membrane potential were investigated. In the plasma of ALS patients, an increase in TBARS and a reduction in GSH and NO were found. In HUVEC/astrocytes treated with a plasma of ALS patients, mitoROS increased, whereas cell viability and mitochondrial membrane potential decreased. Our results show that oxidative stress and NVU play a central role in ALS and suggest that unknown plasma factors could be involved in the disease pathogenesis. Quantifiable changes in ALS plasma related to redox state alterations can possibly be used for early diagnosis. FAU - Grossini, Elena AU - Grossini E AUID- ORCID: 0000-0002-3012-259X AD - Laboratory of Physiology, Department of Translational Medicine, University East Piedmont, 28100 Novara, Italy. FAU - Garhwal, Divya AU - Garhwal D AD - Laboratory of Physiology, Department of Translational Medicine, University East Piedmont, 28100 Novara, Italy. FAU - Venkatesan, Sakthipriyan AU - Venkatesan S AUID- ORCID: 0000-0002-7517-2574 AD - Laboratory of Physiology, Department of Translational Medicine, University East Piedmont, 28100 Novara, Italy. FAU - Ferrante, Daniela AU - Ferrante D AD - Statistic Unit, Department of Translational Medicine, University East Piedmont, 28100 Novara, Italy. FAU - Mele, Angelica AU - Mele A AD - ALS Center, Neurology Unit, Department of Translational Medicine, University East Piedmont, 28100 Novara, Italy. FAU - Saraceno, Massimo AU - Saraceno M AD - ALS Center, Neurology Unit, Department of Translational Medicine, University East Piedmont, 28100 Novara, Italy. FAU - Scognamiglio, Ada AU - Scognamiglio A AD - ALS Center, Neurology Unit, Department of Translational Medicine, University East Piedmont, 28100 Novara, Italy. FAU - Mandrioli, Jessica AU - Mandrioli J AUID- ORCID: 0000-0002-9244-9782 AD - Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy. AD - Neurology Unit, Azienda Ospedaliero Universitaria di Modena, 41126 Modena, Italy. FAU - Amedei, Amedeo AU - Amedei A AUID- ORCID: 0000-0002-6797-9343 AD - Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy. FAU - De Marchi, Fabiola AU - De Marchi F AUID- ORCID: 0000-0003-0197-1880 AD - ALS Center, Neurology Unit, Department of Translational Medicine, University East Piedmont, 28100 Novara, Italy. FAU - Mazzini, Letizia AU - Mazzini L AD - ALS Center, Neurology Unit, Department of Translational Medicine, University East Piedmont, 28100 Novara, Italy. LA - eng PT - Journal Article DEP - 20220317 PL - Switzerland TA - Biomedicines JT - Biomedicines JID - 101691304 PMC - PMC8945260 OTO - NOTNLM OT - astrocytes OT - endothelial cells OT - mitochondria OT - nitric oxide OT - oxidative stress COIS- The authors declare that they have no competing interests. EDAT- 2022/03/26 06:00 MHDA- 2022/03/26 06:01 PMCR- 2022/03/17 CRDT- 2022/03/25 01:04 PHST- 2022/01/24 00:00 [received] PHST- 2022/03/08 00:00 [revised] PHST- 2022/03/14 00:00 [accepted] PHST- 2022/03/25 01:04 [entrez] PHST- 2022/03/26 06:00 [pubmed] PHST- 2022/03/26 06:01 [medline] PHST- 2022/03/17 00:00 [pmc-release] AID - biomedicines10030691 [pii] AID - biomedicines-10-00691 [pii] AID - 10.3390/biomedicines10030691 [doi] PST - epublish SO - Biomedicines. 2022 Mar 17;10(3):691. doi: 10.3390/biomedicines10030691.