BackgroundLysine-specific histone demethylase 1 (LSD1) modulates chromatin status through demethylation of H3K4 and H3K9. It has been demonstrated that LSD1 is hyperphosphorylated and dissociates from chromatin during mitosis. However, the molecular mechanism of LSD1 detachment is unknown.ResultsIn this report, we found that polo-like kinase 1 (PLK1) directly interacted with LSD1 and phosphorylated LSD1 at Ser-126 . Nocodazole-induced metaphase arrest promoted release of LSD1 from chromatin, and the phosphorylation-defective mutant LSD1 (S126A) failed to dissociate from chromatin upon nocodazole treatment.ConclusionsTaken together, our findings demonstrate that phosphorylation of LSD1 at Ser-126 by PLK1 promotes its release from chromatin during mitosis.
Alzheimer’s disease (AD) is the most common type of dementia. Currently, more than 50 million people live with dementia worldwide, and this number is expected to increase. Some of the typical pathological changes of AD include amyloid plaque, hyperphosphorylation of tau protein, secretion of inflammatory mediators, and neuronal apoptosis. Apelin is a neuroprotective peptide that is widely expressed in the body. Among members of apelin family, apelin-13 is the most abundant with a high neuroprotective function. Apelin-13/angiotensin domain type 1 receptor-associated proteins (APJ) system regulates several physiological and pathophysiological cell activities, such as apoptosis, autophagy, synaptic plasticity, and neuroinflammation. It has also been shown to prevent AD development. This article reviews the research progress on the relationship between apelin-13 and AD to provide new ideas for prevention and treatment of AD.
Brain disorders, such as Alzheimer's and Parkinson's disease and cerebral stroke, are an important contributor to mortality and disability worldwide, where their pathogenesis is currently a topic of intense research. The mechanisms underlying the development of brain disorders are complex and vary widely, including aberrant protein aggregation, ischemic cell necrosis and neuronal dysfunction. Previous studies have found that the expression and function of growth differentiation factor-15 (GDF15) is closely associated with the incidence of brain disorders. GDF15 is a member of the TGFβ superfamily, which is a dimer-structured stress-response protein. The expression of GDF15 is regulated by a number of proteins upstream, including p53, early growth response-1, non-coding RNAs and hormones. In particular, GDF15 has been reported to serve an important role in regulating angiogenesis, apoptosis, lipid metabolism and inflammation. For example, GDF15 can promote angiogenesis by promoting the proliferation of human umbilical vein endothelial cells, apoptosis of prostate cancer cells and fat metabolism in fasted mice, and GDF15 can decrease the inflammatory response of lipopolysaccharide-treated mice. The present article reviews the structure and biosynthesis of GDF15, in addition to the possible roles of GDF15 in Alzheimer's disease, cerebral stroke and Parkinson's disease. The purpose of the present review is to summarize the mechanism underlying the role of GDF15 in various brain disorders, which hopes to provide evidence and guide the prevention and treatment of these debilitating conditions.
Purpose To linguistically and culturally adapt the 31-item Singaporean Diabetic Retinopathy Knowledge and Attitudes (DRKA) questionnaire for a Chinese population and assess its reliability and validity using classical and modern psychometric theory. Methods A total of 230 patients with diabetic retinopathy (DR) were recruited, and of these, 202 valid responses were analyzed. Rasch analysis and classical test theory (CTT) methods were used to analyze the fit statistics of the Knowledge ( n = 22 items) and Attitudes ( n = 9 items) scales, including the functionality of the response categories, fit statistics, person and item reliability and separation, unidimensionality, targeting, differential item functioning (DIF), internal consistency, convergent validity, and known-group validity. Results After revision, both the Knowledge and Attitudes scales were unidimensional and had good measurement precision (Person Separation Index = 2.18 and 1.72) and internal consistency (Cronbach's α = 0.83 and 0.82). While the items in the Knowledge scale aptly targeted participants’ ability level, targeting of the Attitudes scale was slightly suboptimal, with items too easy on average for participants’ ability level. There were no issues with DIF and item fit, and the scales showed good known-group validity (scores increased as education level increased) and convergent validity (high correlation with the DRKA Practice questionnaire). Conclusions After a thorough language and cultural verification process, the Chinese version of the DRKA is culturally appropriate and has good psychometric performance. Translational Relevance The DRKA questionnaire may be useful to assess patients’ DR-related knowledge and attitude level, as well as inform specific education interventions and optimize patients' ability to manage their condition.
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