title: CNP and DPYSL2 mRNA expression and promoter methylation levels in brain of Alzheimer's disease patients.
abstract: Alzheimer's disease (AD) is a highly prevalent type of dementia in the elderly population. AD is a complex neurodegenerative disorder. Thus, epigenetic mechanisms that regulate gene expression might have an important role in AD. CNP (2',3'-Cyclic Nucleotide 3' Phosphodiesterase) gene encodes a protein used as an index of myelin alterations. DPYSL2 (Dihydropyrimidinase-like 2) is described as acting in structural and regulatory processes in the central nervous system, such as neural differentiation, neurotransmitter release, and stabilization of microtubules. In this study, we evaluated gene expression and epigenetic regulation of CNP and DPYSL2 genes in three postmortem brain regions (entorhinal and auditory cortices and hippocampus) of AD patients and healthy elderly controls. mRNA quantification was performed using qRT-PCR, and promoter DNA methylation patterns were determined by mass spectrometry using the Sequenom EpiTYPER platform. We observed CNP mRNA downregulation in entorhinal and auditory cortex in relation to the same regions of the control group. CNP alterations in the brain might suggest impairment in myelination leading to a synaptic and cognition loss. No AD-associated differences in CNP and DPYSL2 promoter DNA methylation were observed, suggesting that other mechanisms may be involved in mediating the observed CNP gene expression.
authors.affiliation: Disciplina de Genética, Departamento de Morfologia e Genética, Universidade Federal de São Paulo, São Paulo-SP, Brazil.
authors.forename: Patrícia Natalia
authors.initials: PN
authors.lastname: Silva
authors.forename: Tatiane Katsue
authors.initials: TK
authors.lastname: Furuya
authors.forename: Ianna
authors.initials: I
authors.lastname: Sampaio Braga
authors.forename: Lucas Trevizani
authors.initials: LT
authors.lastname: Rasmussen
authors.forename: Roger Willian
authors.initials: RW
authors.lastname: de Labio
authors.forename: Paulo Henrique
authors.initials: PH
authors.lastname: Bertolucci
authors.forename: Elizabeth Suchi
authors.initials: ES
authors.lastname: Chen
authors.forename: Gustavo
authors.initials: G
authors.lastname: Turecki
authors.forename: Naguib
authors.initials: N
authors.lastname: Mechawar
authors.forename: Spencer Luiz
authors.initials: SL
authors.lastname: Payão
authors.forename: Jonathan
authors.initials: J
authors.lastname: Mill
authors.forename: Marília Cardoso
authors.initials: MC
authors.lastname: Smith
mesh_terms: D063309:2',3'-Cyclic Nucleotide 3'-Phosphodiesterase / Q000235:genetics*; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D001057:Apolipoproteins E / Q000235:genetics; D001483:Base Sequence; D001921:Brain / Q000502:physiology; D019175:DNA Methylation / Q000502:physiology*; D005260:Female; D015870:Gene Expression / Q000502:physiology; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D001057:Apolipoproteins E; D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C095114:collapsin response mediator protein-2; D063309:2',3'-Cyclic Nucleotide 3'-Phosphodiesterase; C571337:CNP protein, human