Analysis of HSPA8 and HSPA9 mRNA expression and promoter methylation in the brain and blood of Alzheimer's disease patients.
Alzheimer's disease (AD) is the most common form of dementia in elderly. Chaperones may have a crucial role in AD due to their involvement in protein quality control, folding, and degradation. In this study, we investigated the mRNA and promoter DNA methylation levels of two chaperones, HSPA8 and HSPA9, in postmortem brain tissue (entorhinal and auditory cortices and hippocampus) from healthy elderly and AD subjects as well as in peripheral blood of healthy elderly and AD patients. mRNA quantification was performed by qRT-PCR and DNA methylation by mass spectrometry. In the peripheral blood, we did not observe a significant difference in HSPA8 and HSPA9 expression between elderly controls and AD. A significant downregulation of HSPA8 and HSPA9 was observed in AD across the three brain regions compared to the controls, suggesting their participation in AD pathogenesis. However, no important DNA methylation differences were observed, suggesting that other mechanism may be involved in controlling these genes expression.
Disciplina de Genética, Departamento de Morfologia e Genética, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil.
Patricia Natalia
PN
Silva
Tatiane Katsue
TK
Furuya
Ianna Lacerda
IL
Braga
Lucas Trevizani
LT
Rasmussen
Roger Willian
RW
Labio
Paulo Henrique
PH
Bertolucci
Elizabeth Suchi
ES
Chen
Gustavo
G
Turecki
Naguib
N
Mechawar
Spencer Luiz
SL
Payão
Jonathan
J
Mill
Marília Cardoso
MC
Smith
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood / Q000235:genetics / Q000473:pathology; D000704:Analysis of Variance; D053327:Apolipoprotein E4 / Q000235:genetics; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D016009:Chi-Square Distribution; D019175:DNA Methylation / Q000502:physiology*; D005260:Female; D050883:HSC70 Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*
D053327:Apolipoprotein E4; D050883:HSC70 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; C494371:HSPA8 protein, human; C492001:HSPA9 protein, human; D024101:Mitochondrial Proteins; D012333:RNA, Messenger
HSPA8; HSPA9; epigenetics; gene expression; mRNA