Plasmodium signal peptide peptidase as a novel antimalarial target

疟原虫信号肽肽酶作为新型抗疟靶点

基本信息

  • 批准号:
    7913568
  • 负责人:
  • 金额:
    $ 40.66万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2009
  • 资助国家:
    美国
  • 起止时间:
    2009-08-21 至 2011-07-31
  • 项目状态:
    已结题

项目摘要

We hypothesize that signal peptide peptidase (SPP) is a superb drug target for pathogenic protozoans, and in particular Plasmodium species that cause malaria. We have obtained data showing that inhibitors of human SPP inhibit P. falciparum SPP (mSPP) and that these SPP inhibitors are capable of killing not only P. falciparum but also other protozoal parasites, T. gondii and T. brucei. Herein we propose to extend these observations to provide the rationale that will spur development of selective P. falciparum SPP (mSPP) inhibitors and provide the tools and infrastructure needed to develop those selective inhibitors. SPP is one member of a family of intramembrane cleaving, aspartyl proteases. In humans SPP and its homologs cleave the transmembrane domain of type II membrane proteins. In contrast, the presenilins (PSs), which are related intramembrane cleaving, aspartyl proteases cleave the transmembrane domain of type I membrane proteins. SPP appears capable of functioning as a protease with out any protein co-factors, whereas PS is catalytically active as a multi-protein complex known as ¿-secretase. PSs have been intensively studies as therapeutic targets in Alzheimer's disease (AD). Indeed, nearly every major pharmaceutical company has had a substantial ¿-secretase inhibitor (GSI) discovery program, and several GSIs are now in human trials. Notably some GSIs are capable of inhibiting the activity of human SPP and mSPP. Humans and other vertebrates express multiple homologues of SPP, while many protozoan parasites such as P. falciparum. T. gondii, C. parvum, G. lamblia, and E. histolytica contain a single SPP gene. Knockout or knockdown of a single SPP gene in C.elegans, Drosophila or Zebrafish results in an embryonic lethal phenotype. Thus, the observation that the protozoan pathogens contain a single member of the SPP protein family offers a compelling reason to hypothesize that inhibition of SPP in these organisms would be lethal and therefore an attractive therapeutic target for a broad range of pathogenic protozoans. Indeed, this hypothesis is strongly supported by our preliminary data. To validate SPP as a viable protein for future antiprotozoal development with a specific focus on the malarial parasite P. falciparum, we will utilize a multifaceted approach using biological, genetic and chemical techniques.
我们推测信号肽肽酶(SPP)是致病性原生动物的一个极好的药物靶点

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Doron Greenbaum其他文献

Doron Greenbaum的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('Doron Greenbaum', 18)}}的其他基金

Cathepsin B Inhibitors as Therapeutics for Ebola Infection
组织蛋白酶 B 抑制剂治疗埃博拉感染
  • 批准号:
    8980049
  • 财政年份:
    2015
  • 资助金额:
    $ 40.66万
  • 项目类别:
CATHEPSIN L INHIBITORS AS PAN-CORONAVIRUS THERAPEUTICS
组织蛋白酶 L 抑制剂作为泛冠状病毒治疗药物
  • 批准号:
    9233899
  • 财政年份:
    2015
  • 资助金额:
    $ 40.66万
  • 项目类别:
CATHEPSIN L INHIBITORS AS PAN-CORONAVIRUS THERAPEUTICS
组织蛋白酶 L 抑制剂作为泛冠状病毒治疗药物
  • 批准号:
    9014497
  • 财政年份:
    2015
  • 资助金额:
    $ 40.66万
  • 项目类别:
CATHEPSIN L INHIBITORS AS PAN-CORONAVIRUS THERAPEUTICS
组织蛋白酶 L 抑制剂作为泛冠状病毒治疗药物
  • 批准号:
    8905856
  • 财政年份:
    2015
  • 资助金额:
    $ 40.66万
  • 项目类别:
A host protein network necessary for parasite cytolysis
寄生虫细胞溶解所需的宿主蛋白网络
  • 批准号:
    8305183
  • 财政年份:
    2012
  • 资助金额:
    $ 40.66万
  • 项目类别:
A host protein network necessary for parasite cytolysis
寄生虫细胞溶解所需的宿主蛋白网络
  • 批准号:
    8415823
  • 财政年份:
    2012
  • 资助金额:
    $ 40.66万
  • 项目类别:
A host protein network necessary for parasite cytolysis
寄生虫细胞溶解所需的宿主蛋白网络
  • 批准号:
    8606155
  • 财政年份:
    2012
  • 资助金额:
    $ 40.66万
  • 项目类别:
Development of an activity based probe family for metallo aminopeptidases
开发基于活性的金属氨肽酶探针家族
  • 批准号:
    8134639
  • 财政年份:
    2010
  • 资助金额:
    $ 40.66万
  • 项目类别:

相似国自然基金

新型F-18标记香豆素衍生物PET探针的研制及靶向Alzheimer's Disease 斑块显像研究
  • 批准号:
    81000622
  • 批准年份:
    2010
  • 资助金额:
    20.0 万元
  • 项目类别:
    青年科学基金项目
阿尔茨海默病(Alzheimer's disease,AD)动物模型构建的分子机理研究
  • 批准号:
    31060293
  • 批准年份:
    2010
  • 资助金额:
    26.0 万元
  • 项目类别:
    地区科学基金项目
跨膜转运蛋白21(TMP21)对引起阿尔茨海默病(Alzheimer'S Disease)的γ分泌酶的作用研究
  • 批准号:
    30960334
  • 批准年份:
    2009
  • 资助金额:
    22.0 万元
  • 项目类别:
    地区科学基金项目

相似海外基金

Pathophysiological mechanisms of hypoperfusion in mouse models of Alzheimer?s disease and small vessel disease
阿尔茨海默病和小血管疾病小鼠模型低灌注的病理生理机制
  • 批准号:
    10657993
  • 财政年份:
    2023
  • 资助金额:
    $ 40.66万
  • 项目类别:
Social Connectedness and Communication in Parents with Huntington''s Disease and their Offspring: Associations with Psychological and Disease Progression
患有亨廷顿病的父母及其后代的社会联系和沟通:与心理和疾病进展的关联
  • 批准号:
    10381163
  • 财政年份:
    2022
  • 资助金额:
    $ 40.66万
  • 项目类别:
The Role of Menopause-Driven DNA Damage and Epigenetic Dysregulation in Alzheimer s Disease
更年期驱动的 DNA 损伤和表观遗传失调在阿尔茨海默病中的作用
  • 批准号:
    10531959
  • 财政年份:
    2022
  • 资助金额:
    $ 40.66万
  • 项目类别:
The Role of Menopause-Driven DNA Damage and Epigenetic Dysregulation in Alzheimer s Disease
更年期驱动的 DNA 损伤和表观遗传失调在阿尔茨海默病中的作用
  • 批准号:
    10700991
  • 财政年份:
    2022
  • 资助金额:
    $ 40.66万
  • 项目类别:
Interneurons as early drivers of Huntington´s disease progression
中间神经元是亨廷顿病进展的早期驱动因素
  • 批准号:
    10518582
  • 财政年份:
    2022
  • 资助金额:
    $ 40.66万
  • 项目类别:
Interneurons as Early Drivers of Huntington´s Disease Progression
中间神经元是亨廷顿病进展的早期驱动因素
  • 批准号:
    10672973
  • 财政年份:
    2022
  • 资助金额:
    $ 40.66万
  • 项目类别:
Social Connectedness and Communication in Parents with Huntington''s Disease and their Offspring: Associations with Psychological and Disease Progression
患有亨廷顿病的父母及其后代的社会联系和沟通:与心理和疾病进展的关联
  • 批准号:
    10585925
  • 财政年份:
    2022
  • 资助金额:
    $ 40.66万
  • 项目类别:
Oligodendrocyte heterogeneity in Alzheimer' s disease
阿尔茨海默病中的少突胶质细胞异质性
  • 批准号:
    10180000
  • 财政年份:
    2021
  • 资助金额:
    $ 40.66万
  • 项目类别:
Serum proteome analysis of Alzheimer´s disease in a population-based longitudinal cohort study - the AGES Reykjavik study
基于人群的纵向队列研究中阿尔茨海默病的血清蛋白质组分析 - AGES 雷克雅未克研究
  • 批准号:
    10049426
  • 财政年份:
    2021
  • 资助金额:
    $ 40.66万
  • 项目类别:
Repurposing drugs for Alzheimer´s disease using a reverse translational approach
使用逆翻译方法重新利用治疗阿尔茨海默病的药物
  • 批准号:
    10295809
  • 财政年份:
    2021
  • 资助金额:
    $ 40.66万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了