title: Brain-derived neurotrophic factor expression increases after enzyme replacement therapy in Gaucher disease.
abstract: Mutations in the GBA gene are related to an increased risk of developing neurodegenerative diseases. The exact molecular mechanisms involved in the interaction between GBA and α-synuclein, a protein that has been associated with several neurological diseases, remain unsolved. Brain-derived neurotrophic factor (BDNF) is a neurotrophin that is important for the normal development of the peripheral and central nervous system, and it plays a key role in neuronal survival and synaptic plasticity in the adult brain. A reduction in BDNF expression has been reported in patients with Parkinson's disease, Alzheimer's disease and dementia with Lewy bodies. We analyzed BDNF levels in the plasma of Gaucher Disease (GD) patients who were not being treated with enzyme replacement therapy (ERT) and then subsequently following ERT; we compared the levels to those of healthy controls. We demonstrated that BDNF levels were remarkably diminished in GD patients who were under no specific treatment and these levels increased following ERT. This is the first study that demonstrates a variation in the plasma levels of a neurotrophic factor in GD type 1 patients. Further studies are required to correlate BDNF level variations with the clinical findings and the response to therapy in GD patients. Low levels of BDNF are associated with neurodegenerative diseases; therefore, BDNF could provide a new therapeutic target for GD patients with neurological symptoms.
authors.affiliation: Medical Genetics Service, Hospital de Clinicas de Porto Alegre, Brazil; Post Graduation Program of Genetics and Molecular Biology, Universidade Federal do Rio Grande do Sul, Brazil; BRAIN Laboratory, Hospital de Clínicas de Porto Alegre, Brazil. Electronic address: fvairo@hcpa.ufrgs.br.
authors.forename: Filippo
authors.initials: F
authors.lastname: Vairo
authors.affiliation: Post Graduation Program of Genetics and Molecular Biology, Universidade Federal do Rio Grande do Sul, Brazil; BRAIN Laboratory, Hospital de Clínicas de Porto Alegre, Brazil.
authors.forename: Fernanda
authors.initials: F
authors.lastname: Sperb-Ludwig
authors.affiliation: Medical Genetics Service, Hospital de Clinicas de Porto Alegre, Brazil.
authors.forename: Matheus
authors.initials: M
authors.lastname: Wilke
authors.affiliation: Medical Genetics Service, Hospital de Clinicas de Porto Alegre, Brazil.
authors.forename: Kristiane
authors.initials: K
authors.lastname: Michellin-Tirelli
authors.affiliation: Medical Genetics Service, Hospital de Clinicas de Porto Alegre, Brazil.
authors.forename: Cristina
authors.initials: C
authors.lastname: Netto
authors.affiliation: CTN - Centro de Triagem Neonatal, Porto Alegre, Brazil.
authors.forename: Eurico Camargo
authors.initials: EC
authors.lastname: Neto
authors.affiliation: Medical Genetics Service, Hospital de Clinicas de Porto Alegre, Brazil; BRAIN Laboratory, Hospital de Clínicas de Porto Alegre, Brazil; Department of Genetics, Universidade Federal do Rio Grande do Sul, Brazil.
authors.forename: Ida Vanessa
authors.initials: IV
authors.lastname: Doederlein Schwartz
mesh_terms: D000328:Adult; D019208:Brain-Derived Neurotrophic Factor / Q000097:blood*; D056947:Enzyme Replacement Therapy / Q000379:methods*; D005260:Female; D005776:Gaucher Disease / Q000097:blood* / Q000628:therapy*; D005962:Glucosylceramidase / Q000627:therapeutic use*; D006801:Humans; D008297:Male
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D005962:Glucosylceramidase
keywords: BDNF; Enzyme replacement therapy; Gaucher disease