Discovery of functionally selective Alzheimer's disease therapeutics

发现功能选择性阿尔茨海默病疗法

基本信息

项目摘要

Abstract The prevalence of Alzheimer's disease (AD) and the associated financial and caregiver burden is projected to escalate dramatically unless disease-modifying treatments are discovered. Our research is focused on addressing this urgent unmet medical and societal need through the discovery and development of pharmacotherapies capable of averting or delaying the progression of AD. Brain inflammation initiated by chronic oxidative-nitrosative stress is a proven component of the pathogenic cascade leading to mild cognitive impairment (MCI) and AD. When surplus inflammatory nitric oxide and superoxide molecules combine they form the brain-impairing reactive species peroxynitrite. This perpetuates inflammation resulting in the progressive neurodegeneration observed in AD. Our innovative approach consists of managing two processes associated with inflammatory disease progression. The first involves interrupting the cycle of peroxynitrite generation by suppressing unsafe elevations in nitric oxide triggered by oxidative stress, and the second involves enhancing resilience to and recovery from inflammatory insults by facilitating the secretion of brain-derived neurotrophic factor (BDNF). A single stress-activated chaperone protein is mechanistically capable of both mediating BDNF secretion and regulating nitric oxide levels under proinflammatory conditions. Preliminary studies have identified chemotype starting points for further CNS drug development which have the desired dual functional selectivity profile for this target receptor. Our plan is to optimize the CNS drug-like properties of these functionally selective chemotypes with the goal of developing medicines that can significantly modify the course of MCI/AD.
摘要

项目成果

期刊论文数量(0)
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ROBERT R LUEDTKE其他文献

ROBERT R LUEDTKE的其他文献

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{{ truncateString('ROBERT R LUEDTKE', 18)}}的其他基金

D3 Receptor Compounds for the Treatment of Psychostimulant Abuse
用于治疗精神兴奋剂滥用的 D3 受体化合物
  • 批准号:
    7676618
  • 财政年份:
    2007
  • 资助金额:
    $ 54.46万
  • 项目类别:
D3 Receptor Compounds for the Treatment of Psychostimulant Abuse
用于治疗精神兴奋剂滥用的 D3 受体化合物
  • 批准号:
    8069685
  • 财政年份:
    2007
  • 资助金额:
    $ 54.46万
  • 项目类别:
D3 Receptor Compounds for the Treatment of Psychostimulant Abuse
用于治疗精神兴奋剂滥用的 D3 受体化合物
  • 批准号:
    8135269
  • 财政年份:
    2007
  • 资助金额:
    $ 54.46万
  • 项目类别:
D3 Receptor Compounds for the Treatment of Psychostimulant Abuse
用于治疗精神兴奋剂滥用的 D3 受体化合物
  • 批准号:
    7676010
  • 财政年份:
    2007
  • 资助金额:
    $ 54.46万
  • 项目类别:
D3 Receptor Compounds for the Treatment of Psychostimulant Abuse
用于治疗精神兴奋剂滥用的 D3 受体化合物
  • 批准号:
    7842065
  • 财政年份:
    2007
  • 资助金额:
    $ 54.46万
  • 项目类别:
D3 Receptor Compounds for the Treatment of Psychostimulant Abuse
用于治疗精神兴奋剂滥用的 D3 受体化合物
  • 批准号:
    9011513
  • 财政年份:
    2007
  • 资助金额:
    $ 54.46万
  • 项目类别:
D3 Receptor Compounds for the Treatment of Psychostimulant Abuse
用于治疗精神兴奋剂滥用的 D3 受体化合物
  • 批准号:
    7346814
  • 财政年份:
    2007
  • 资助金额:
    $ 54.46万
  • 项目类别:
D3 Receptor Compounds for the Treatment of Psychostimulant Abuse
用于治疗精神兴奋剂滥用的 D3 受体化合物
  • 批准号:
    7501481
  • 财政年份:
    2007
  • 资助金额:
    $ 54.46万
  • 项目类别:
D3 Receptor Compounds for the Treatment of Psychostimulant Abuse
用于治疗精神兴奋剂滥用的 D3 受体化合物
  • 批准号:
    7919465
  • 财政年份:
    2007
  • 资助金额:
    $ 54.46万
  • 项目类别:
D3 Receptor Compounds for the Treatment of Psychostimulant Abuse
用于治疗精神兴奋剂滥用的 D3 受体化合物
  • 批准号:
    9185279
  • 财政年份:
    2007
  • 资助金额:
    $ 54.46万
  • 项目类别:

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