Alzheimer’s disease (AD) is characterized by the development of amyloid plaques and neurofibrillary tangles (NFTs) consisting of aggregated β-amyloid (Aβ) and tau, respectively. The amyloid hypothesis has been the predominant framework for research in AD for over two decades. According to this hypothesis, the accumulation of Aβ in the brain is the primary factor initiating the pathogenesis of AD. However, it remains elusive what factors initiate Aβ aggregation. Studies demonstrate that AD has multiple causes, including genetic and environmental factors. Furthermore, genetic factors, many age-related events and pathological conditions such as diabetes, traumatic brain injury (TBI) and aberrant microbiota also affect the aggregation of Aβ. Here we provide an overview of the age-related early events and other pathological processes that precede Aβ aggregation.

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As a result of various stresses, lesions caused by DNA-damaging agents occur constantly in each cell of the human body. Generally, DNA damage is recognized and repaired by the DNA damage response (DDR) machinery, and the cells survive. When repair fails, the genomic integrity of the cell is disrupted—a hallmark of cancer. In addition, the DDR plays a dual role in cancer development and therapy. Cancer radiotherapy and chemotherapy are designed to eliminate cancer cells by inducing DNA damage, which in turn can promote tumorigenesis. Over the past two decades, an increasing number of microRNAs (miRNAs), small noncoding RNAs, have been identified as participating in the processes regulating tumorigenesis and responses to cancer treatment with radiation therapy or genotoxic chemotherapies, by modulating the DDR. The purpose of this review is to summarize the recent findings on how miRNAs regulate the DDR and discuss the therapeutic functions of miRNAs in cancer in the context of DDR regulation.

BackgroundMicroRNA-720 (miR-720), a nonclassical miRNA, is involved in the initiation and progression of several tumors. In our previous studies, miR-720 was shown to be significantly upregulated in cervical cancer tissues compared with normal cervical tissues. However, the precise biological functions of miR-720, and its molecular mechanisms of action, are still unknown.ResultsMicroarray expression profiles, luciferase reporter assays, and western blot assays were used to validate Rab35 as a target gene of miR-720 in HEK293T and HeLa cells. The regulation of Rab35 expression by miR-720 was assessed using qRT-PCR and western blot assays, and the effects of exogenous miR-720 and Rab35 on cell migration were evaluated in vitro using Transwell® assay, wound healing assay, and real-time analyses in HeLa cells. The influences of exogenous miR-720 on cell proliferation were evaluated in vitro by the MTT assay in HeLa cells. In addition, expression of E-cadherin and vimentin associated with epithelial-mesenchymal transition were also assessed using western blot analyses after transfection of miR-720 mimics and Rab35 expression vectors. The results showed that the small GTPase, Rab35, is a direct functional target of miR-720 in cervical cancer HeLa cells. By targeting Rab35, overexpression of miR-720 resulted in a decrease in E-cadherin expression and an increase in vimentin expression and finally led to promotion of HeLa cell migration. Furthermore, reintroduction of Rab35 3′-UTR(−) markedly reversed the induction of cell migration in miR-720-expressing HeLa cells.ConclusionsThe miR-720 promotes cell migration of HeLa cells by downregulating Rab35. The results show that miR-720 is a novel cell migration-associated gene in cervical cancer cells.Electronic supplementary materialThe online version of this article (doi:10.1186/s13578-015-0047-5) contains supplementary material, which is available to authorized users.

The pathological hallmarks of Parkinson's disease (PD) are the progressive loss of dopaminergic neurons in the substantia nigra and the formation of Lewy bodies (LBs) in remaining neurons. LBs primarily consist of aggregated α-Synuclein (α-Syn). However, accumulating evidence suggests that Tau, which is associated with tauopathies such as Alzheimer’s disease (AD), progressive supranuclear palsy (PSP), and argyrophilic grain disease, is also involved in the pathophysiology of PD. A genome-wide association study (GWAS) identified MAPT, the gene encoding the Tau protein, as a risk gene for PD. Autopsy of PD patients also revealed the colocalization of Tau and α-Syn in LBs. Experimental evidence has shown that Tau interacts with α-Syn and influences the pathology of α-Syn in PD. In this review, we discuss the structure and function of Tau and provide a summary of the current evidence supporting Tau’s involvement as either an active or passive element in the pathophysiology of PD, which may provide novel targets for the early diagnosis and treatment of PD.