Alzheimer's disease (AD), the most common form of dementia in the aged population, presents an increasing clinical challenge in terms of diagnosis and treatment. Neurodegeneration is one of the hallmarks of AD, which consequently induces cognitive impairment. Brainderived neurotrophic
factor (BDNF), a neuroprotective factor, has been implicated in neuronal survival and proliferation. The epigenetic mechanism of BDNF methylation may be responsible for the reduced expression of BDNF in patients with AD. DNA methyltransferase may contribute to the methylation of BDNF, which
is involved in neuroprotection in AD. In addition, epigenetic modifications, including a combination of microRNAs (miRNAs/miRs) and DNA methylation, have been suggested as regulatory mechanisms in the control of neuronal survival. In the present study, the expression of miR29c was determined
in the cerebrospinal fluid (CSF) of patients with AD and of healthy control individuals. A marked decrease in the expression of miR29c was observed in the AD group compared with the normal control group, accompanied by a decreased in the expression of BDNF. Additionally, a significant increase
in the expression of DNA methyltransferase 3 (DNMT3) was observed in the CSF from the patients with AD. Correlation analysis revealed that the expression of miR29c was positively correlated with BDNF and negatively correlated with DNMT3 protein in the CSF of patients with AD. In addition,
the regulatory association between miR29c, DNMT3 and BDNF were also examined in vitro. It was demonstrated that miR29c directly targeted DNMT3 and contributed to neuronal proliferation by regulating the expression of BDNF, at least partially, through enhancing the activity of the tyrosine
receptor kinase B/extracellular signalregulated kinase signaling pathway. In conclusion, the present study suggested that miR29c may be a promising potential therapeutic target in the treatment of AD.
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Document Type: Research Article
Department of Neurology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China
Department of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, P.R. China
Department of Neurology, Haikou People's Hospital, Haikou, Hainan 570208, P.R. China
Publication date: January 1, 2015
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Molecular Medicine Reports is a monthly, peer-reviewed journal available in print and online, that includes studies devoted to molecular medicine, underscoring aspects including pharmacology, pathology, genetics, neurosciences, infectious diseases, molecular cardiology and molecular surgery. In vitro and in vivo studies of experimental model systems pertaining to the mechanisms of a variety of diseases offer researchers the necessary tools and knowledge with which to aid the diagnosis and treatment of human diseases.
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