Progress in Chemistry

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Molecular Recognition and Self-assembly in Chemical Biology

Shen Jiacong^{1,2 *} Wu Yuqing¹

Progress in Chemistry. 2007, 19(012): 1839-1843.

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Shen Jiacong^{1,2 *} Wu Yuqing¹
. Molecular Recognition and Self-assembly in Chemical Biology[J]. Progress in Chemistry, 2007, 19(012): 1839-1843.

The merge of chemistry and biology opens a new subject of chemical biology, extending new field for human to reveal the nature of life at molecule level. Molecular recognition and self-assembly are always the fundament of information storage, duplication and transferring in nature, and therefore based on this, the fabrication of specific supramolecular systems with target biological functions will be crucial important in revealing the nature and process of life. Based on our previous studies, three concerning fields are summarized in the present paper: (1) The mimic of glutathione peroxide (GPX) and the recognition between it and substrate; (2) Tissue regeneration material and bioactivated scaffold; (3) self-assembly and disassembly of virus-like particle (VLP).
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DNA Interactions with Ruthenium(II) Polypyridyl Complexes

Chao Hui^** 　Gao Feng 　Ji Liangnian^**

Progress in Chemistry. 2007, 19(012): 1844-1851.

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Chao Hui^** 　Gao Feng 　Ji Liangnian^**. DNA Interactions with Ruthenium(II) Polypyridyl Complexes[J]. Progress in Chemistry, 2007, 19(012): 1844-1851.

DNA is the carrier of genetic information and the material basis of gene expression, The interaction between metal complexes and DNA has received intense interest and become an important research field of bioionrganic chemistry. This review highlights some recent progresses in the studies of DNA recognition, cleavage and topoisomerase inhibition with ruthenium(II) polypyridyl complexes.
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Novel Concepts and Approach of Immunoassay and Cellular Analysis

Yan Feng¹ Ju Huangxian^2**

Progress in Chemistry. 2007, 19(012): 1852-1860.

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Yan Feng¹ Ju Huangxian^2**.
Novel Concepts and Approach of Immunoassay and Cellular Analysis
[J]. Progress in Chemistry, 2007, 19(012): 1852-1860.

The development of novel concepts and approach for clinic detection by combining analytical chemistry with clinic diagnosis has become one of research frontiers for need of human health. In this filed immunoassay, especially the development of multianalyte immunoassay methods, and cellular detection have attracted considerable attention. This review focuses on the research progress in these areas in recent three years. The new concepts in immunoassay, including separation-free, quasi-reagentless and reagentless amperometric immunoassay, multichannel amperometric immunochips based on separated immunoreaction areas, flow-through multianalyte chemiluminescent immunosensing systems based on substrate zone resolution, channel resolution and channel and substrate zone two-dimensional resolution, and new approach in cytosensing for electrochemically detecting cell concentration and amount on electrode surface, monitoring interfacial adhesion, proliferation and apoptosis of cells, studying exogenous effect and viability of living cells, and anti-tumor drug sensitivity test, are simply summarized, and their applications in clinic diagnosis of cancer disease are also discussed.
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Fluorescent Semiconductor Quantum Dots for Biolabeling^*

Lin Yi, Xie Haiyan, Zhang Zhiling, Tian Zhiquan, Pang Daiwen^**

Progress in Chemistry. 2007, 19(012): 1861-1865.

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Lin Yi, Xie Haiyan, Zhang Zhiling, Tian Zhiquan, Pang Daiwen^**. Fluorescent Semiconductor Quantum Dots for Biolabeling^*[J]. Progress in Chemistry, 2007, 19(012): 1861-1865.

In-situ, ultra-sensitive, real-time and dynamic acquisition of biochemical information of life is one of the pending key problems for bioscience. It is crucial to develop new related methodologies for life sciences. Fluorescent semiconductor quantum dots bring opportunities to the field, whose novel fluorescence properties are attracting more and more interest. However, some problems involved in quantum dot applications still need to be solved, including controllable solubilization of quantum dots, orientation of biomolecules on their surfaces, and the stability and specificity of quantum dot-labeled bioprobes etc. This review comments briefly on the labeling technique based on quantum dots, construction of quantum dot-labeled bioprobes and their application in biomedical fields.
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Chemical Synthesis of Proteins

Li Juan^1,2 Zheng Jishen¹ Shen Fei¹ Fang Gemin¹ Guo Qingxiang² Liu Lei^1,2**

Progress in Chemistry. 2007, 19(012): 1866-1882.

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Li Juan^1,2 Zheng Jishen¹ Shen Fei¹ Fang Gemin¹ Guo Qingxiang² Liu Lei^1,2**. Chemical Synthesis of Proteins[J]. Progress in Chemistry, 2007, 19(012): 1866-1882.

Proteins that contain non-natural amino acid residues (such as post-translationally modified proteins and proteins functionalized with synthetic probes) are highly important molecules in chemical biology. These molecules cannot be readily obtained through biological expression, so that the only approach to produce them is to use chemical synthesis. Currently the most important method in the field of protein chemical synthesis is cysteine-based native chemical ligation, which can efficiently condense peptide segments in aqueous solutions under mild conditions to generate natural as well as non-natural proteins. Here we systematically reviewed the fundamental aspects of cysteine-based native chemical ligation. We also surveyed the very recent progresses in this field to improve the efficiency and scope of this particular ligation method. Finally, the representative applications of the ligation method in the synthesis of natural proteins, lapidated proteins, and glycoproteins were reviewed.
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Design, Synthesis and Biological Activity of novel Steroidal Bioconjugates

Jin Peiyuan, Ju Yong^**

Progress in Chemistry. 2007, 19(012): 1883-1895.

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Jin Peiyuan, Ju Yong^**. Design, Synthesis and Biological Activity of novel Steroidal Bioconjugates[J]. Progress in Chemistry, 2007, 19(012): 1883-1895.

Steroids play very important role in the life of animals and plants and are also important biological molecules. Due to their lipophilic character, membrane affinity, and the ability of binding to low density lipoproteins, design and synthesis of steroidal bioconjugates become more important. It should be increased lipophilicity and enhanced permeability through cell membranes and favorable specific organ distribution, and have shown many pharmacological activities, such as, potent antimicrobial, analgesic, anti-inflammatory, and anti-tumor activities etc. In this review, the recent development of biologically important steroidal bioconjugates is briefly summarized, including steroid-drug conjugates, steroidal derivatives containing phosphorus, ionophores and molecular carriers, and the dimmers of steroids.
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Oligosaccharide Synthesis by Pre-Activation Strategy

Geng Yiqun, Ye Xinshan^**

Progress in Chemistry. 2007, 19(012): 1896-1902.

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Geng Yiqun, Ye Xinshan^**. Oligosaccharide Synthesis by Pre-Activation Strategy[J]. Progress in Chemistry, 2007, 19(012): 1896-1902.

The multifaceted biological importance of oligosaccharides and glycoconjugates has made them very popular synthetic targets in modern synthetic chemistry. Great progress has been made in the construction of complex oligosaccharides based on a variety of synthetic strategies. Among these strategies, the one-pot glycosylation is very attractive and shows great promise for assembly of oligosaccharide libraries and automated synthesis. Traditional one-pot glycosylation approach based on the chemoselective principle or orthogonal strategy needs extensive protecting group manipulations and/or aglycon adjustments for designing building blocks with suitable anomeric reactivities. The recently established pre-activation strategy has some advantages over the traditional one-pot glycosylation approach, since it does not require the tuning of the building blocks in an armed-disarmed fashion. The latest advances in one-pot oligosaccharide synthesis by pre-activation strategy will be summarized in this review.
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Advance in Dynamic Combinatorial Chemistry

Chen Yuyan, Liu Gang^**

Progress in Chemistry. 2007, 19(012): 1903-1908.

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Chen Yuyan, Liu Gang^**. Advance in Dynamic Combinatorial Chemistry[J]. Progress in Chemistry, 2007, 19(012): 1903-1908.

Dynamic combinatorial chemistry (DCC), a new branch of combinatorial chemistry, will have important role in the drug lead discovery. DCC makes use of reversible bond-forming reactions to create thermodynamically controlled library. Upon addition of a target molecule, the molar fractions of individual library member are perturbed as a function of their affinity to the target. The review includes the character and classification of DCC, the reversible covalent reactions involved in DCC, the advance in the screening method and the application of DCC in the novel lead drug discovery.
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The Interaction of Macrocyclic Polyamine derivatives and Their Complexes with DNA

Zhou Lihong, Wang Na, Yu Xiaoqi^*

Progress in Chemistry. 2007, 19(012): 1909-1918.

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Zhou Lihong, Wang Na, Yu Xiaoqi^*. The Interaction of Macrocyclic Polyamine derivatives and Their Complexes with DNA[J]. Progress in Chemistry, 2007, 19(012): 1909-1918.

In this paper, the development of the interaction of macrocyclic polyamine derivatives and their complexes with DNA was reviewed. The focuses are especially on some research and findings about the interactions of macrocyclic polyamine mononuclear, dinuclear, functionalized complexes and cyclen-based polymers with DNA in our research group. In addition, the application of these complexes on chemical nuclease was discussed in brief. In mono-, dinuclear macrocyclic polyamine metal complexes, we synthesized a series of mononuclear cyclen containing pyridine, benzene, imidazole, triazole complexes, and dinuclear macrocyclic polyamine metal complexes linked with rigid spacers and flexible spacers respectively. Moreover, the interactions of these complexes with plasmid DNA were also investigated, the results showed that dinuclear cyclen metal complexes linked with rigid spacers can catalyze the cleavage of plasmid DNA at low concentration within shorter time. Secondly, the syntheses of functionalized macrocyclic polyamine complexes containing nucleobases, PNA monomer, imidazolium side, crown ether, ferrocenyl side and their interaction with DNA were studies, respectively. Finally, in multinuclear macrocyclic polyamine derivatives, we found that cyclen-based oligomers form polymer complex with DNA, thus protect DNA from enzymatic degradation efficiently.
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Biocatalysis for Green Chemistry and Drug Development

Zhenming Chen¹, Jinhua Liu ², Tao, Junhua^2,3**

Progress in Chemistry. 2007, 19(012): 1919-1927.

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Zhenming Chen¹, Jinhua Liu ², Tao, Junhua^2,3**. Biocatalysis for Green Chemistry and Drug Development[J]. Progress in Chemistry, 2007, 19(012): 1919-1927.

Biocatalysis is becoming a transformational technology for chemical synthesis as a result of recent breakthroughs in biotechnology – exponential growth in publically available sequences from the gene database and protein data bank (PDB), efficient molecular cloning and protein expression platforms, powerful directed enzyme evolution technologies to improve biocatalyst’s specificity, selectivity and stability[1]. In this review, the focus will be directed to its applications in drug manufacturing to deliver cost-effective chemoenzymatic processes, green chemistry to minimize the generation of wastes and usage of hazardous reagents, and natural product modification to discover novel therapeutics with improved biological profiles.
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Progress in Selenoenzyme Mimics

Liu Junqiu^*, Luo Guimin, Shen Jiacong

Progress in Chemistry. 2007, 19(012): 1928-1938.

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Liu Junqiu^*, Luo Guimin, Shen Jiacong. Progress in Selenoenzyme Mimics[J]. Progress in Chemistry, 2007, 19(012): 1928-1938.

Selenium, an essential trace element, has a long history of association with human health and diseases and exerts its important biological role as selenocysteine residue in selenoproteins. To exploration of the structural and functional importance of selenium in selenoproteins and for the potential applications in the development of selenium related medicine, significant efforts have been made in selenoprotein biomimetic chemistry. Because of the unique redox properties of selenium in mammalian selenoenzyme glutathione peroxidase (GPX), a number of organoselenium/tellurium compounds and selenoproteins were developed to mimic the native GPx. Herein, several strategies containing chemical and biological techniques or the combination of both for the redesign of selenoenzyme structure and function have been reviewed.
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Discovering Potential Drug Leads via Docking, Synthesis and Bioassay

Ye Deju¹, Luo Xiaomin¹, Shen Jianhua¹, Zhu Weiliang¹, Shen Xu^1,2, Jiang Hualiang^1,2, Liu Hong^1**

Progress in Chemistry. 2007, 19(012): 1939-1946.

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Ye Deju¹, Luo Xiaomin¹, Shen Jianhua¹, Zhu Weiliang¹, Shen Xu^1,2, Jiang Hualiang^1,2, Liu Hong^1**
. Discovering Potential Drug Leads via Docking, Synthesis and Bioassay[J]. Progress in Chemistry, 2007, 19(012): 1939-1946.

Discovering potential drug leads has played a key role in the drug development. As a new method or technology for drug discovery, virtual screening via molecular docking has been developed as a practical tool complemented with high throughput empirical screening, and is now a widespread drug lead identification method in the pharmaceutical industry. In this review, we will introduce recent advances in discovering drug leads via docking, synthesis and bioassay focused on our laboratory work.
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Biocatalysis in Drug Discovery and Development

Chen Yijun^* Wu Xuri

Progress in Chemistry. 2007, 19(012): 1947-1954.

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Chen Yijun^* Wu Xuri. Biocatalysis in Drug Discovery and Development[J]. Progress in Chemistry, 2007, 19(012): 1947-1954.

Due to the advantages including mild conditions, high catalytic efficiency, high stereoselectivity and regioselectivity and less byproducts, biocatalysis has been widely utilized and applied in drug discovery and development. Moreover, biocatlysts can be structurally changed and optimized through new technologies such as directed evolution, which could be better suited for biocatalytic processes. In this review, recent progress in the field of application of biocatalysis in drug discovery and development is briefly introduced and discussed.
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Small Molecules Targeting Tumor Apoptosis Related Proteins and Genes

Fan Jian,Zhang Hualin, Tan Chunyan, Jiang Yuyang^**

Progress in Chemistry. 2007, 19(012): 1955-1964.

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Fan Jian,Zhang Hualin, Tan Chunyan, Jiang Yuyang^**. Small Molecules Targeting Tumor Apoptosis Related Proteins and Genes[J]. Progress in Chemistry, 2007, 19(012): 1955-1964.

The regulation of apoptosis, which attracts more and more attention recently, has been used as an emerging strategy to develop new cancer therapies. The structures, functions, and regulating mechanisms of several major targets in apoptosis, including Bcl-2, p53, TRAIL, IAP and Caspases, are discussed as they might be successful cancer therapeutic targets. Additionally, the latest progress of small molecules which target apopsotis is summerized.
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Using Small Molecules on Surfaces to Control Cell Adhesion

Liu Dingbin^1,2, Xie Yunyan², Shao Huawu^1*, Jiang Xingyu^2*

Progress in Chemistry. 2007, 19(012): 1965-1971.

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Liu Dingbin^1,2, Xie Yunyan², Shao Huawu^1*, Jiang Xingyu^2*. Using Small Molecules on Surfaces to Control Cell Adhesion[J]. Progress in Chemistry, 2007, 19(012): 1965-1971.

Cell adhesion is an important physiological process; most types of metazoic cells rely on adhesion to surfaces to carry out their functions. The adhesion of mammalian cells requires the presence of surface-immobilized molecules as ligands, in most cases, proteins or peptide mimics thereof, that bind to receptors on the cell membrane. The binding between these ligands and receptors promotes the adhesion of cells. Polyethyleneglycol (PEG) can resist cell adhesion. We use these small molecules to modulate cell adhesion on surfaces. Cell motility is a dynamic process in which the binding between extracellular ligands and receptors on cell membrane undergo regulation in time and space. This review introduces several newly developed tools using small molecules on surfaces and microfabrication to control cell adhesion and motility.
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Michael Reaction Acceptor Molecule in Chemical Biology

Zhao Qinshi^1*, Cong Yuwen²

Progress in Chemistry. 2007, 19(012): 1972-1976.

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Zhao Qinshi^1*, Cong Yuwen². Michael Reaction Acceptor Molecule in Chemical Biology[J]. Progress in Chemistry, 2007, 19(012): 1972-1976.

Michael reaction acceptors are the functionalities in which the olefins or acetylenes conjugated to electron-withdrawing groups. The compounds with Michael acceptors, taking Michael reaction with nucleophile, are called as Michael reaction acceptor molecule. Michael reaction acceptor molecules are considered as a class of biological activity molecule which directly or indirectly involved in the life processes. They are also regulators in many signaling pathway in cells. Thus they have played an important role in chemical biology studies. This review covers the progress of Michael reaction acceptors molecules in chemical biology.
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Structure-Activity Relationship Studies of Neuropeptide FF

Fang Quan, Zhang Bangzhi, Wang Rui^**

Progress in Chemistry. 2007, 19(012): 1977-1985.

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Fang Quan, Zhang Bangzhi, Wang Rui^**. Structure-Activity Relationship Studies of Neuropeptide FF[J]. Progress in Chemistry, 2007, 19(012): 1977-1985.

Peptides play pivotal roles in contolling and modulating the physiological functions. More and more attention has focused on the subject of peptides due to its facilities of chemical synthesis and modification. Neuropeptide FF (NPFF), an important opioid-modulating peptide, mediates a variety of biological actions, such as opioid tolerance and abstinence. However, to date, the potent and highly selective agonists and antagonists for NPFF receptors are still lacking, which hamper studies of the pharmcological activities of NPFF. This paper introduces the finding of NPFF, and reviews the progress on the precursors, the receptors and the bio-activities of NPFF in recent years. The structrue-activitiy relationship studies of NPFF are espe-cially described. Authors’ work in studying of the effects of chemical modifications of NPFF on the pharm-cological activities is referred. The research trends for the future are proposed.
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Molecular Mechanism of Iron Transport Mediated by Iron-containing Proteins

Sun Xuesong, He Qingyu^*

Progress in Chemistry. 2007, 19(012): 1986-1990.

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Sun Xuesong, He Qingyu^*. Molecular Mechanism of Iron Transport Mediated by Iron-containing Proteins[J]. Progress in Chemistry, 2007, 19(012): 1986-1990.

Iron, an essential element for virtually all organisms, is required as a cofactor for many enzymes that are involved in various cellular functions ranging from respiration to DNA replication. On the other hand, iron is also toxic when in excess of cellular homeostasis due to the generation of hydroxyl radicals through Fenton reaction. Organisms have developed mechanisms to control cellular iron levels by closely modulating the iron uptake, storage and efflux. DMT1 (divalent metal transpoter), ferroportin, hephaestin are involved in intenstinal iron absorption. Transferrin and transferrin receptor participate in cellular iron uptake and transport, whereas ferritin functions as an iron strorage protein, and IRP (iron responsive protein) regulates iron metabolism. This review focuses on the mechanisms of iron transport mediated by these iron-containing proteins.
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Matrix Metalloproteinase Inhibitors from Natural Product

Fang Xuexun* Yang Jingang Shi Xiujuan

Progress in Chemistry. 2007, 19(012): 1991-1998.

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Fang Xuexun* Yang Jingang Shi Xiujuan. Matrix Metalloproteinase Inhibitors from Natural Product[J]. Progress in Chemistry, 2007, 19(012): 1991-1998.

Matrix metalloproteinases (MMPs) play key roles in a number of pathological processes and matrix metalloproteinase inhibitors have been developed with the aim of becoming pharmaceutical drugs. In this paper we have reviewed the development history of MMP inhibitors and the new concepts for the designed and development of the MMP inhibitors. We focus on the enzymatic MMP inhibitors and inhibitors of the MMPs transcription from natural sources. In addition, the anti-cancer activities of these MMP inhibitors were also discussed.
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Studies of Inducible DNA Cross-Linking Agents

Weng Xiaocheng, Weng Liwei, Bai Minghui, Zhou Yangyang, Zhou Xiang**

Progress in Chemistry. 2007, 19(012): 1999-2005.

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Weng Xiaocheng, Weng Liwei, Bai Minghui, Zhou Yangyang, Zhou Xiang**. Studies of Inducible DNA Cross-Linking Agents[J]. Progress in Chemistry, 2007, 19(012): 1999-2005.

Selectively destroy the DNA of the tumor cells by induction has been arosed many attention for medicinal application. Inducible DNA cross-linking agents have provided a promising method for these researches. As the improving the selectivity of the targets induced by various methods, such as oxidation, reduction and light-induction to cross-link DNA, they hold great importance on clinic therapy. This paper has reported and summarized the most recent advances on inducible DNA cross-linking agents.
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Advances in Research of Apolipoprotein E and Alzheimer’s Disease

Liu Qian, Wu Weihui, Li Renwang, Zheng Yizhe, Zhao Yufen, Li Yanmei**

Progress in Chemistry. 2007, 19(012): 2006-2012.

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Liu Qian, Wu Weihui, Li Renwang, Zheng Yizhe, Zhao Yufen, Li Yanmei**. Advances in Research of Apolipoprotein E and Alzheimer’s Disease[J]. Progress in Chemistry, 2007, 19(012): 2006-2012.

The apolipoprotein E(apoE) type 4 allele(ApoE4) is a highly susceptibility gene for late-onset familial and sporadic Alzheimer disease.Both the major pathologic hallmarks:β-amyliod plaque and Neurofibrilary tangles(NFTs) are related to ApoE,of which the main function in Alzheimer’s disease and the recent advances in potential related drugs domestic and abroad are discussed.
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Small Molecule Autophagy Inducers: A New Therapeutic Paradigm for Neural Degeneration Diseases

Yang Wenjun, Wen Longping*

Progress in Chemistry. 2007, 19(012): 2013-2016.

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Yang Wenjun, Wen Longping*. Small Molecule Autophagy Inducers: A New Therapeutic Paradigm for Neural Degeneration Diseases[J]. Progress in Chemistry, 2007, 19(012): 2013-2016.

Intracellular accumulation of altered and misfolded proteins is the basis of most neural degeneration diseases. A novel path for therapy of neural degeneration diseases was offered by the application of small molecule, which enhances the clearance of aggregate-prone proteins through inducing autophagy. In this review we introduce the pathogenesis of neural degeneration diseases, the mechanism of autophagy and the effect in neural degeneration diseases.

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