Pub Date : 2004-02-29DOI: 10.2174/1568013043483202
Scott C. Johns, Kari J Furtek, D. Looney
{"title":"Chemotherapy of Human Immunodeficiency Virus Infection","authors":"Scott C. Johns, Kari J Furtek, D. Looney","doi":"10.2174/1568013043483202","DOIUrl":"https://doi.org/10.2174/1568013043483202","url":null,"abstract":"","PeriodicalId":88234,"journal":{"name":"Current medicinal chemistry. Immunology, endocrine & metabolic agents","volume":"4 1","pages":"27-47"},"PeriodicalIF":0.0,"publicationDate":"2004-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568013043483202","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67897419","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2004-02-29DOI: 10.2174/1568013043483149
Z. Bánki, D. Wilflingseder, C. Ammann, M. Dierich, H. Stoiber
{"title":"Innate Immunity: Helping Hand for HIV Infection?","authors":"Z. Bánki, D. Wilflingseder, C. Ammann, M. Dierich, H. Stoiber","doi":"10.2174/1568013043483149","DOIUrl":"https://doi.org/10.2174/1568013043483149","url":null,"abstract":"","PeriodicalId":88234,"journal":{"name":"Current medicinal chemistry. Immunology, endocrine & metabolic agents","volume":"4 1","pages":"13-20"},"PeriodicalIF":0.0,"publicationDate":"2004-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568013043483149","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67897879","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2004-02-29DOI: 10.2174/1568013043483167
Gary L. Buchschacher and
{"title":"Molecular Basis of Human Immunodeficiency Virus Type 1 as Both Target and Tool for Clinical Gene Therapy","authors":"Gary L. Buchschacher and","doi":"10.2174/1568013043483167","DOIUrl":"https://doi.org/10.2174/1568013043483167","url":null,"abstract":"","PeriodicalId":88234,"journal":{"name":"Current medicinal chemistry. Immunology, endocrine & metabolic agents","volume":"4 1","pages":"1-11"},"PeriodicalIF":0.0,"publicationDate":"2004-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568013043483167","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67897408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2004-02-29DOI: 10.2174/1568013043483211
E. Tacconelli, A. Savarino, F. Bernardis, R. Cauda, Antonio Cassone
{"title":"Candidiasis and HIV-Protease Inhibitors: The Expected and the Unexpected","authors":"E. Tacconelli, A. Savarino, F. Bernardis, R. Cauda, Antonio Cassone","doi":"10.2174/1568013043483211","DOIUrl":"https://doi.org/10.2174/1568013043483211","url":null,"abstract":"","PeriodicalId":88234,"journal":{"name":"Current medicinal chemistry. Immunology, endocrine & metabolic agents","volume":"4 1","pages":"49-59"},"PeriodicalIF":0.0,"publicationDate":"2004-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568013043483211","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67897427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2003-11-30DOI: 10.2174/1568013033483258
M. Goedert
{"title":"Relevance of Mutations in Tau for Understanding the Tauopathies","authors":"M. Goedert","doi":"10.2174/1568013033483258","DOIUrl":"https://doi.org/10.2174/1568013033483258","url":null,"abstract":"","PeriodicalId":88234,"journal":{"name":"Current medicinal chemistry. Immunology, endocrine & metabolic agents","volume":"3 1","pages":"341-348"},"PeriodicalIF":0.0,"publicationDate":"2003-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67895219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2003-11-30DOI: 10.2174/1568013033483276
C. Curtain, K. Barnham, A. Bush
Over a decade of studies have pointed to metal mediated neural oxidative damage as an attractive target for the treatment of Alzheimer’s disease. Because of the nature of the blood brain barrier, systemic depletion of the metals, copper, zinc and possibly iron, is not a viable approach. However preliminary studies with CQ, a blood brain barrier penetrating chelating agent, are showing promise. CQ probably works by combining with the metal centres, primarily copper and zinc complexes of Aβ, in the neuropil. This review discusses some of the background that resulted in CQ becoming a lead compound and how we might advance our understanding of its action METALLOPROTEINS AND OXIDATION DAMAGE IN ALZHEIMER’S DISEASE Increasing evidence emphasises the importance of metals in neurobiology. For example, copper-binding proteins in the central nervous system may possess oxidant or anti-oxidant properties, possibly affecting neuronal function or triggering neurodegeneration. Among the copper-binding proteins related to neurodegenerative disease is the amyloid precursor protein (APP) of Alzheimer’s disease (AD) that has two copper-binding sites APP135-156, and near its N-terminus, APP1. APP is a highly conserved and widely expressed integral membrane protein with a single membrane-spanning domain. The amyloid β peptides (Aβ) are 39–43 residue polypeptides derived from proteolytic cleavage of APP, by the combined action of two proteases, BACE and γsecretase. A characteristic central nervous system histological marker in AD patients is accumulation of morphologically heterogeneous neuritic plaques and cerebrovascular deposits of Aβ [1]. Both the APP135 – 156 and As have been shown to have copper reducing activity with concomitant production of reactive oxygen species (ROS) [2, 3]. It has been long-established that oxidative damage to many classes of biological molecule, including sugars, lipids, proteins and nucleic acids, is increased in AD [4-6]. Cu and Fe interact with Aβ to make it toxic in cell culture. In vitro Aβ catalyses H2O2 generation through the reduction of Cu and Fe, using O2 and biological reducing agents, such as cholesterol, vitamin C and catecholamines, as substrates [710]. Consistent with these biochemical properties being responsible for disease, the neurotoxicity of Aβ in culture is mediated by the Aβ:Cu (or Aβ:Fe) forming H2O2 [8, 11]. *Address correspondence to this author at the Laboratory for Oxidation Biology, Genetics and Aging Research Unit, Massachusetts General Hospital East, Bldg 114, 16 Street, Charlestown, MA 02129, USA; Tel: 617-726-8244; Fax: 617-724-1823; E-mail: bush@helix.mgh.harvard.edu Aβ generation alone was once believed to engender toxicity. However, we found that Aβ was not toxic in the absence of Cu or Fe [3]. Although there have been reports of toxic fibrillar and toxic soluble oligomeric species of As, those studies have not yet excluded the possibility that the toxicity of the modified As species is dependent upon
{"title":"Aβ Metallobiology and the Development of Novel Metal-Protein Attenuating Compounds (MPACs) for Alzheimers Disease","authors":"C. Curtain, K. Barnham, A. Bush","doi":"10.2174/1568013033483276","DOIUrl":"https://doi.org/10.2174/1568013033483276","url":null,"abstract":"Over a decade of studies have pointed to metal mediated neural oxidative damage as an attractive target for the treatment of Alzheimer’s disease. Because of the nature of the blood brain barrier, systemic depletion of the metals, copper, zinc and possibly iron, is not a viable approach. However preliminary studies with CQ, a blood brain barrier penetrating chelating agent, are showing promise. CQ probably works by combining with the metal centres, primarily copper and zinc complexes of Aβ, in the neuropil. This review discusses some of the background that resulted in CQ becoming a lead compound and how we might advance our understanding of its action METALLOPROTEINS AND OXIDATION DAMAGE IN ALZHEIMER’S DISEASE Increasing evidence emphasises the importance of metals in neurobiology. For example, copper-binding proteins in the central nervous system may possess oxidant or anti-oxidant properties, possibly affecting neuronal function or triggering neurodegeneration. Among the copper-binding proteins related to neurodegenerative disease is the amyloid precursor protein (APP) of Alzheimer’s disease (AD) that has two copper-binding sites APP135-156, and near its N-terminus, APP1. APP is a highly conserved and widely expressed integral membrane protein with a single membrane-spanning domain. The amyloid β peptides (Aβ) are 39–43 residue polypeptides derived from proteolytic cleavage of APP, by the combined action of two proteases, BACE and γsecretase. A characteristic central nervous system histological marker in AD patients is accumulation of morphologically heterogeneous neuritic plaques and cerebrovascular deposits of Aβ [1]. Both the APP135 – 156 and As have been shown to have copper reducing activity with concomitant production of reactive oxygen species (ROS) [2, 3]. It has been long-established that oxidative damage to many classes of biological molecule, including sugars, lipids, proteins and nucleic acids, is increased in AD [4-6]. Cu and Fe interact with Aβ to make it toxic in cell culture. In vitro Aβ catalyses H2O2 generation through the reduction of Cu and Fe, using O2 and biological reducing agents, such as cholesterol, vitamin C and catecholamines, as substrates [710]. Consistent with these biochemical properties being responsible for disease, the neurotoxicity of Aβ in culture is mediated by the Aβ:Cu (or Aβ:Fe) forming H2O2 [8, 11]. *Address correspondence to this author at the Laboratory for Oxidation Biology, Genetics and Aging Research Unit, Massachusetts General Hospital East, Bldg 114, 16 Street, Charlestown, MA 02129, USA; Tel: 617-726-8244; Fax: 617-724-1823; E-mail: bush@helix.mgh.harvard.edu Aβ generation alone was once believed to engender toxicity. However, we found that Aβ was not toxic in the absence of Cu or Fe [3]. Although there have been reports of toxic fibrillar and toxic soluble oligomeric species of As, those studies have not yet excluded the possibility that the toxicity of the modified As species is dependent upon ","PeriodicalId":88234,"journal":{"name":"Current medicinal chemistry. Immunology, endocrine & metabolic agents","volume":"3 1","pages":"309-315"},"PeriodicalIF":0.0,"publicationDate":"2003-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67896369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2003-11-30DOI: 10.2174/1568013033483311
D. Walsh, D. Hartley, D. Selkoe
{"title":"The Many Faces of A: Structures and Activity","authors":"D. Walsh, D. Hartley, D. Selkoe","doi":"10.2174/1568013033483311","DOIUrl":"https://doi.org/10.2174/1568013033483311","url":null,"abstract":"","PeriodicalId":88234,"journal":{"name":"Current medicinal chemistry. Immunology, endocrine & metabolic agents","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2003-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67896502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2003-11-30DOI: 10.2174/1568013033483285
D. Howlett
Misfolding of newly formed proteins not only results in a loss of physiological function of the protein but also may lead to the intraor extracellular accumulation of that protein. A number of diseases have been shown to be characterised by the accumulation of misfolded proteins, notable examples being Alzheimer's disease and the tauopathies. The obvious inference is that these proteinaceous deposits are pathogenic features of the disease. However, systems such as the unfolded protein response and ubiquitin-proteasome complex are in place in the cell to target misfolded proteins for degradation and clearance. Evidence suggests that in disease states, these protein-handling systems may be overwhelmed and the misfolded proteins accumulate as either extracellular deposits (eg. senile plaques in Alzheimer's disease) or intracellular inclusions (as in Lewy bodies in Parkinson's disease). These accumulations may be the direct cause of the particular pathology associated with the diseases or they may be inert "packages" designed to protect the cell from toxic insult.
{"title":"Protein Misfolding in Disease: Cause or Response?","authors":"D. Howlett","doi":"10.2174/1568013033483285","DOIUrl":"https://doi.org/10.2174/1568013033483285","url":null,"abstract":"Misfolding of newly formed proteins not only results in a loss of physiological function of the protein but also may lead to the intraor extracellular accumulation of that protein. A number of diseases have been shown to be characterised by the accumulation of misfolded proteins, notable examples being Alzheimer's disease and the tauopathies. The obvious inference is that these proteinaceous deposits are pathogenic features of the disease. However, systems such as the unfolded protein response and ubiquitin-proteasome complex are in place in the cell to target misfolded proteins for degradation and clearance. Evidence suggests that in disease states, these protein-handling systems may be overwhelmed and the misfolded proteins accumulate as either extracellular deposits (eg. senile plaques in Alzheimer's disease) or intracellular inclusions (as in Lewy bodies in Parkinson's disease). These accumulations may be the direct cause of the particular pathology associated with the diseases or they may be inert \"packages\" designed to protect the cell from toxic insult.","PeriodicalId":88234,"journal":{"name":"Current medicinal chemistry. Immunology, endocrine & metabolic agents","volume":"3 1","pages":"371-383"},"PeriodicalIF":0.0,"publicationDate":"2003-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67896484","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2003-11-30DOI: 10.2174/15680134103030400II
D. Howlett
{"title":"Preface [Hot topic: Protein Misfolding in the Amyloidoses and other Disorders (Guest Editor: David R. Howlett)]","authors":"D. Howlett","doi":"10.2174/15680134103030400II","DOIUrl":"https://doi.org/10.2174/15680134103030400II","url":null,"abstract":"","PeriodicalId":88234,"journal":{"name":"Current medicinal chemistry. Immunology, endocrine & metabolic agents","volume":"3 1","pages":"1-2"},"PeriodicalIF":0.0,"publicationDate":"2003-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/15680134103030400II","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"67899981","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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