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    • ATP binding cassette transporters such as

    2019-09-07

    ATP-binding cassette transporters such as ABCA1 and ABCG1 are expressed on cell membranes to transport cholesterol from CI 976 to HDL. These transporters help to improve RCT and reduce atherosclerosis. ABCA1 and ABCG1 gene expression are primarily induced by the stimulation of liver X receptor/retinoid X receptor (LXR/RXR) axis, which is stimulated by cholesterol accumulation in the cells (Favari et al., 2015). LXR binds to the LXREs in the promoter of ABCG1 gene thereby activating its transcription (Zhang et al., 2016). Our study revealed that inhibiting ERK up-regulated ABCA1 and ABCG1 without increasing the expression of LXR-α. To examine this phenomenon in more detail, we used ChIP to detect LXRE binding with LXR-α. We found inhibiting ERK increased the interaction between LXR protein and the LXRE without increasing the amount of LXR-α. Together, we therefore concluded that inhibiting ERK increased ABCG1 expression by improving the binding of LXR-α to LXREs rather than through increased LXR-α expression. In vivo, T cell functional phenotypes alter their relative ability to function as regulatory or inflammatory in response to environmental clues. Different T cell functional phenotypes could play different roles in atherosclerosis. An increase in the ratio of Teff to regulator T Cells (Treg) promotes atherosclerosis (Tabas and Lichtman, 2017). We found ZAP70-deficiency improves cholesterol efflux capacity and reduces inflammatory response of T cells. ZAP70-deficiency probably have influence on atherosclerosis owing to these effect. However, the effects of ZAP70-deficiency on neither ratio of Teff to Treg nor atherosclerosis in vivo were not investigated in this paper. In the future, our group may continue to detect the effects of ZAP70-deficiency in vivo.
    Acknowledgements This work was supported by the Science and Technology Foundation of Guangzhou City of China (2015010090), the Major Scientific Research Foundation of Colleges and Universities of Guangdong Provience (2016KZDXM016), the Clinical Training Foundation of Southern Medical University (LC2016PY002), and the Innovative Foundation of Guangdong Province of China (2014KZDXM020).
    Introduction Neurodegenerative diseases refer to the progressive loss of the structure and/or function of neurons. The disease is characterized by an accumulation of protein aggregation, disturbing the normal function of the central nervous system (CNS). To date, many diseases have been linked to neurodegeneration including Alzheimer\'s disease (AD), Huntington\'s disease (HD), Parkinson\'s disease (PD), frontotemporal dementia, amyotrophic lateral sclerosis, spinocerebellar ataxia, (Gitler et al., 2017), prion diseases (Peden and Ironside, 2012), Hereditary spastic paraplegia, Friedreich\'s ataxia (FRDA), and Optic atrophy type 1 (Lin and Beal, 2006). As longevity has raised worldwide, the incidence of age-related neurodegenerative disease such as AD, PD, etc. has also increased. Both genetic and environmental factors have been implicated in the induction and progression of neurodegenerative diseases (Kumar et al., 2016; Rasool et al., 2014; Tewari et al., 2018; Wong and Cuervo, 2010). Neurodegenerative diseases such as AD and PD, share a variety of common characteristics at both cellular and subcellular levels. Studies on the biological molecular and intracellular pathways revealed that the cytosol and endoplasmic reticulum play pivotal roles in production of novel structural and functional protein molecules. In nature, signal transduction pathways are highly complicated. For example, disturbance of protein aggregation (Kumar et al., 2016) or autophagy (Wong and Cuervo, 2010) can result in a remarkable degenerative disorder. Empowering of the endogenous defense system against oxidative stress through dietary intervention could be a plausible therapeutic strategy. All over the world, scientists are seeking to find future drugs either within the traditional medicinal plants or in plant derived natural compounds, which both are among the essential resources of complementary and alternative medicine. Herbal based natural products are able to act synergistically in combination with other components of the same plant and also could enhance the pharmacological effects of the synthetic drugs, even counteract their toxic actions (Sofowora et al., 2013). Many chemicals, such as phenolic compounds, are strong radical scavengers able to alleviate oxidative stress associated neurodegeneration (Kita et al., 2014). Dietary antioxidants, especially polyphenols, are being considered as a promising approach to prevent or slow the pathological development of neurological illness and aging (Farzaei et al., 2017; Frandsen and Narayanasamy, 2018; Suganthy et al., 2016). In brain stem review, we summarized a detailed profile on the proven clinical efficacy of different flavonoids and polyphenols in several types of neurodegenerative diseases. In addition, the role of ERK signaling pathway as potential target of flavonoids-based therapy in neurodegenerative diseases has been discussed.