title: Serum Markers of Neurodegeneration in Maple Syrup Urine Disease.
abstract: Maple syrup urine disease (MSUD) is an inherited disorder caused by deficient activity of the branched-chain α-keto acid dehydrogenase complex involved in the degradation pathway of branched-chain amino acids (BCAAs) and their respective α-keto-acids. Patients affected by MSUD present severe neurological symptoms and brain abnormalities, whose pathophysiology is poorly known. However, preclinical studies have suggested alterations in markers involved with neurodegeneration. Because there are no studies in the literature that report the neurodegenerative markers in MSUD patients, the present study evaluated neurodegenerative markers (brain-derived neurotrophic factor (BDNF), cathepsin D, neural cell adhesion molecule (NCAM), plasminogen activator inhibitor-1 total (PAI-1 (total)), platelet-derived growth factor AA (PDGF-AA), PDGF-AB/BB) in plasma from 10 MSUD patients during dietary treatment. Our results showed a significant decrease in BDNF and PDGF-AA levels in MSUD patients. On the other hand, NCAM and cathepsin D levels were significantly greater in MSUD patients compared to the control group, while no significant changes were observed in the levels of PAI-1 (total) and PDGF-AB/BB between the control and MSUD groups. Our data show that MSUD patients present alterations in proteins involved in the neurodegenerative process. Thus, the present findings corroborate previous studies that demonstrated that neurotrophic factors and lysosomal proteases may contribute, along with other mechanisms, to the intellectual deficit and neurodegeneration observed in MSUD.
authors.affiliation: Laboratório de Bioenergética e Núcleo de Excelência em Neurociências Aplicadas de Santa Catarina (NENASC), Programa de Pós-Graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense, Av. Universitária, 1105, Criciúma, SC, 88806-000, Brazil.
authors.forename: Giselli
authors.initials: G
authors.lastname: Scaini
authors.affiliation: Department of Genetics, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.
authors.forename: Tássia
authors.initials: T
authors.lastname: Tonon
authors.affiliation: Medical Genetics Service, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil.
authors.forename: Carolina F Moura
authors.initials: CFM
authors.lastname: de Souza
authors.affiliation: Laboratório de Erros Inatos do Metabolismo, Programa de Pós-Graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brazil.
authors.forename: Patricia F
authors.initials: PF
authors.lastname: Schuk
authors.affiliation: Laboratório de Neuroquímica, Instituto de Biofísica Carlos Chagas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Gustavo C
authors.initials: GC
authors.lastname: Ferreira
authors.affiliation: Hospital Sirio Libanes, São Paulo, Brazil.
authors.forename: Joao Seda
authors.initials: JS
authors.lastname: Neto
authors.affiliation: Associação de Pais e Amigos dos Excepcionais (APAE), Salvador, Brazil.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Amorin
authors.affiliation: Department of Genetics, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Brazil.|Medical Genetics Service, Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil.
authors.forename: Ida Vanessa D
authors.initials: IVD
authors.lastname: Schwartz
authors.affiliation: Laboratório de Bioenergética e Núcleo de Excelência em Neurociências Aplicadas de Santa Catarina (NENASC), Programa de Pós-Graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense, Av. Universitária, 1105, Criciúma, SC, 88806-000, Brazil. emiliostreck@gmail.com.
authors.forename: Emilio L
authors.initials: EL
authors.lastname: Streck
mesh_terms: D015415:Biomarkers / Q000378:metabolism*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D016923:Cell Death; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008375:Maple Syrup Urine Disease / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000378:metabolism
chemical_list: D015415:Biomarkers; D019208:Brain-Derived Neurotrophic Factor; D017395:Plasminogen Activator Inhibitor 1; D010982:Platelet-Derived Growth Factor; C075278:platelet-derived growth factor A; C095477:platelet-derived growth factor AB
keywords: Brain-derived neurotrophic factor (BDNF); Cathepsin D; Maple syrup urine disease; Neural cell adhesion molecule (NCAM); Neurodegeneration; Platelet-derived growth factor AA (PDGF-AA)