+ Site Statistics
+ Search Articles
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ PDF Full Text
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Translate
+ Recently Requested

Role of the Long Non-Coding RNA MAPT-AS1 in Regulation of Microtubule Associated Protein Tau (MAPT) Expression in Parkinson's Disease

Role of the Long Non-Coding RNA MAPT-AS1 in Regulation of Microtubule Associated Protein Tau (MAPT) Expression in Parkinson's Disease

Plos One 11(6): E0157924

Studies investigating the pathogenic role of the microtubule associated protein tau (MAPT) gene in Parkinson's disease (PD) have indicated that DNA methylation of the promoter region is aberrant in disease, leading to dysregulated MAPT expression. We examined two potential regulators of MAPT gene expression in respect to PD, a promoter-associated long non-coding RNA MAPT-AS1, and DNA methyltransferases (DNMTs), enzymes responsible for new and maintenance of DNA methylation. We assessed the relationship between expression levels of MAPT and the candidate MAPT-AS1, DNMT1, DNMT3A and DNMT3B transcripts in four brain regions with varying degrees of cell loss and pathology (putamen, anterior cingulate cortex, visual cortex and cerebellum) in N = 10 PD and N = 10 controls. We found a significant decrease in MAPT-AS1 expression in PD (p = 7.154 x 10-6). The transcript levels of both MAPT-AS1 (p = 2.569 x 10-4) and DNMT1 (p = 0.001) correlated with those of MAPT across the four brain regions, but not with each other. Overexpression of MAPT-AS1 decreased MAPT promoter activity by ∼2.2 to 4.3 fold in an in vitro luciferase assay performed in two cell lines (p ≤ 2.678 x 10-4). Knock-down expression of MAPT-AS1 led to a 1.3 to 6.3 fold increase in methylation of the endogenous MAPT promoter (p ≤ 0.011) and a 1.2 to 1.5 fold increased expression of the 4-repeat MAPT isoform transcript (p ≤ 0.013). In conclusion, MAPT-AS1 and DNMT1 have been identified as potential epigenetic regulators of MAPT expression in PD across four different brain regions. Our data also suggest that increased MAPT expression could be associated with disease state, but not with PD neuropathology severity.

(PDF emailed within 0-6 h: $19.90)

Accession: 058791109

Download citation: RISBibTeXText

PMID: 27336847

DOI: 10.1371/journal.pone.0157924

Related references

Role of the H1 haplotype of microtubule-associated protein tau (MAPT) gene in Greek patients with Parkinson's disease. Bmc Neurology 9: 26, 2009

Microtubule-associated protein tau (MAPT) influences the risk of Parkinson's disease among Indians. Neuroscience Letters 460(1): 16-20, 2009

The estrogen receptor influences microtubule-associated protein tau (MAPT) expression and the selective estrogen receptor inhibitor fulvestrant downregulates MAPT and increases the sensitivity to taxane in breast cancer cells. Breast Cancer Research 12(3): R43, 2010

Association of microtubule associated protein tau/Saitohin (MAPT/STH) MAPT_238bp/STH Q7R polymorphisms and Parkinson's disease: A meta-analysis. Biochemical and Biophysical Research Communications 453(3): 653-661, 2015

Association of MAPT haplotypes with Alzheimer's disease risk and MAPT brain gene expression levels. Alzheimer's Research and Therapy 6(4): 39, 2014

The role of CDK5 and GSK3B kinases in hyperphosphorylation of microtubule associated protein tau (MAPT) in Alzheimer's disease. Bioinformation 9(20): 1023-1030, 2014

The effect of age and the H1c MAPT haplotype on MAPT expression in human brain. Neurobiology of Aging 30(10): 1652-1656, 2008

Regulation of microtubule-associated protein tau (MAPT) by miR-34c-5p determines the chemosensitivity of gastric cancer to paclitaxel. Cancer ChemoTherapy and Pharmacology 71(5): 1159-1171, 2013

Knockdown of LncRNA MAPT-AS1 inhibites proliferation and migration and sensitizes cancer cells to paclitaxel by regulating MAPT expression in ER-negative breast cancers. Cell and Bioscience 8: 7, 2018

Dementia risk in Parkinson disease: disentangling the role of MAPT haplotypes. Archives of Neurology 68(3): 359-364, 2011

Haplotypes and gene expression implicate the MAPT region for Parkinson disease: the GenePD Study. Neurology 71(1): 28-34, 2008

The role of SNCA and MAPT in Parkinson disease and LRRK2 parkinsonism in the Tunisian Arab-Berber population. European Journal of Neurology 21(11): E91-E92, 2014

Interactions between Microtubule-Associated Protein Tau (MAPT) and Small Molecules. Cold Spring Harbor Perspectives in Medicine 7(7), 2016

Investigating the role of rare coding variability in Mendelian dementia genes (APP, PSEN1, PSEN2, GRN, MAPT, and PRNP) in late-onset Alzheimer's disease. Neurobiology of Aging 35(12): 2881.E1-2881.E6, 2015

Regional expression of the MAPT gene is associated with loss of hubs in brain networks and cognitive impairment in Parkinson disease and progressive supranuclear palsy. Neurobiology of Aging 48: 153-160, 2016