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The technology of network analysis,based on a variety of disciplines theory,is the core technology in the research of network pharmacology,through which we can mine specified information from molecular networks from multi-angle and multi-level. It has been used to investigate and obtain valuable information about the ingredients/drugs with specific pharmacological effects ,the key nodes,modules and motifs with specific biological function,and physiological mechanism of drug action,pathogenesis of dis?ease,or biomarker of disease,especially for the complex disease represented by Alzheimer′s disease(AD). In this paper,the general techniques of network analysis in network pharmacology study are reviewed.
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Luteinizing hormone(LH)is a gonadotropin of hypothalamic-pituitary-gonadal axis(HPG),secreted by the anteri?or pituitary. The secretion of LH is directly controlled by the release of gonadotropin releasing hormone(GnRH),acts at the ovaries and testes to stimulate the production of gonadal hormones. Aging leads to increases in LH,and higher serum levels of LH has been ob?served in Alzheimer′s disease(AD)patients when compared to age-matched controls. Evidences from basic research and epidemiologi?cal investigation support the critical role of elevated LH in pathogenic process of AD and deteriorating cognitive decline. Here we sum?marize the recent discoveries containing human AD epidemiological evidence for LH,cognitive impairments resulting from LH activi?ty,LH in AD pathology and LH receptor signaling mechanisms.
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Network construction technology is the basis for network pharmacology research. Data originated from experiment, database and computational prediction can be used to construct drugome network,diseaseome network and molecular interactome net?work. The molecular network construction for the complex diseases represented by Alzheimer′s disease(AD)could be used to identify the important targets,pathogenesis and drug action mechanism,and guide drug development and drug reposition. This paper reviews techniques for molecular network construction in network pharmacology study.
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β-secretase, a typeⅠtransmembrane aspartic protease, initiates β-amyloid protein(Aβ) formation by cleaving β-amyloid precursor protein between Met596 and Asp597 or between Tyr606 and Glu607 to generate N-terminal fragment of Aβ. β-Secretase has many members,and aspartic proteinaseβ-site amyloid precursor protein-cleaving enzyme 1 (BACE1) is the most famous of them. Because BACE1 plays a significant role in the pathogenesis of Alzheimer′s disease (AD) and a neurodegenerative disease, it has been studied fully. In this article, we review the gene and protein structure, transcription and translation, intracellular trafficking and metabolism of BACE1 and summarize substrates and homologous enzymes of BACE1. This work provides some reference for BACE1 as a drug target on AD.
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Technologies for glycomics usually involve methods for separation and purification of poly-saccharides, and separation, structure resolution, quantification, property investigation and function comment of glycan chains. Because of the different biochemical properties of glycoproteins, proteogly-cans and glycolipids, the separation and purification of polysaccharides involve corresponding fractional precipitation, boric acid affinity, titanium dioxide, affinity chromatography, size exclusion method, and gel filtration chromatography column chromatography methods. The lectins, water affinity chromatogra-phy , solid phase extraction and other technologies could be applied to the oil enrichment of high pure and specific glycan chains. The structure of glycan chains can be analyzed using lectin microarray technolo-gy, mass spectrometry, and derivatization markers of glycan chains. lsotope labelling and metabolic labeling can be used to quantify glycan chains. The glycan biological function can be better understood using glycan chain structure analysis software and database of glycan chains by bioinformatics.
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Aim To disclose the molecular mechanism of Liuwei Dihuang decoction(LW)enhances the cognitive function of central nervous system, the effects of Liuwei Dihuang decoction on the differential expression genes in the hippocampus of senescence-accelerated mouse was studied. Methods There were 8 gene expression patterns, such as SAMP8 and SAMR1, SAMP8 as negative control and SAMR1 as positive control, huperzine A-treated SAMP8 and SAMP8 as negative control, LW-treated SAMP8 and SAMP8 as negative control, were compared and assessed by use of the differential expression cDNA microarray of the hippocampus of SAMP8 and SAMR1. The response genes of LW were compared. Results LW had significant modulating effects on some of the gene expressions. Expressions of genes, such as DUSP12, NSF, STUB1, CaMKⅡ?, AMFR, UQCRFS1 and other 11 novel genes without any functional clues changed significantly. These genes involved in the protein-tyrosine phosphatase family, the AAA(ATPases associated with diverse cellular activities)gene family, the serine/threonine protein kinases family, ubiquitin ligase, mitochondrial function and so on. Conclusions These results suggested LW effects on the cognitive impairments might be multi-mechanism and these genes might be the potential gene targets for LW effects on the impairments.
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Vesicular glutamate transporters(VGLUTs)package specifically glutamate into synaptic vesicles in the presynaptic terminal for subsequent release into the synaptic cleft.VGLUT1 and VGLUT2 together label all glutamatergic neurons,are highly specific markers of glutamatergic neurons and their axon terminals.VGLUT1 and VGLUT2 are respectively the neurochemical marker of cortico-cortical projection and thalamo-cortical projection.VGLUT3 is also expressed in cholinergic interneurons,serotoninergic neurons,subsets of GABAergic interneurons in the hippocampus and cerebral cortex.The disfunction of VGLUTs can lead to the abnormal excitatory neurotransmitter glutamate,resulting in many nervous system disease.In order to give a clue for prevention and therapy of these diseases,this paper reviews the disfunction of VGLUTs effects on Alzheimer's disease(AD),Parkinson's disease(PD),schizophrenia,depressive disorder,epilepsy and deafness.
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Objective To investigate the clinical forensic assessment on cases of suspected medical malpractice and the other related aspects concerning the assessment in clinical forensic expertise. Methods Clinical data from 25 cases expertized for suspicion of medical malpractice were retrospectively analyzed. Results 16 cases were due to the medical muff (10 cases of 16 medical muff had a bad consequence and happened in the department of operation, 6 cases had not ones); 9 cases were non-medical muff. Conclusion Though the medical muff recognized is basic, but the relationship between the medical muff and the following bad results of medical muff is the best key for the forensic expertise. Otherwise, the scientific and practical value must be considered in the forensic expertise.
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The Eph protein family,consisting of Eph receptors and their corresponding membrane-anchored protein ligands-Ephrin,is no doubt the largest receptor protein tyrosine kinases family till now.Interactions between Eph receptors and Ephrin ligands based on their special structure might make the Eph protein family one of new targets of disease′s treatment and consequently studies related to Eph proteins and their receptors have draw more and more attention.This overview will focus on recent progresses in the classification,gene expression,protein structure,function and protein-receptor interactions of the Eph protein family and their receptors.Much of the focus of this overview is on their physiological and pathophysiological role in nervous system and their therapeutic perspective from several aspects.