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Infection01:20

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When a pathogen enters the body and reproduces, it can cause an infection, damage body cells, and cause illness symptoms that eventually lead to disease. Therefore, its prevention requires breaking the chain of infection.
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Cystic fibrosis (CF), an autosomal recessive disorder, significantly affects the function of exocrine glands. This genetically inherited disease is characterized by the production of thick and sticky mucus, which can severely affect various organs and systems in the body.
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Stages of infection describe what happens to a susceptible host once a pathogen invades the human body. The stages of infection are incubation, prodromal, illness, stage of decline, and convalescence. The incubation stage is the period from exposure to a pathogen until symptoms start. The infected person is unaware of impending illness as the pathogens grow and multiply within the body. The duration may vary depending on the type of infection. The incubation period of measles averages ten to...
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基礎科学と病態生理

Zeynep Sarica1, Kevin P Kotredes1, Alaina M Reagan1

  • 1The Jackson Laboratory, Bar Harbor, ME, USA.

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まとめ
この要約は機械生成です。

ヒトのアルツハイマー病リスク遺伝子とヒ素曝露を組み込んだ新規マウスモデルは、late-onset Alzheimer 病(LOAD)をより良く模倣する。これらのモデルは、ヒト LOAD と類似の脳の変化を示し、バイオマーカーおよび治療標的の発見を助ける。

キーワード:
late-onset Alzheimer 病マウスモデルヒ素曝露MTHFRバイオマーカー治療標的

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科学分野:

  • 神経科学
  • 遺伝学
  • 毒物学

背景:

  • 現在のマウスモデルは、late-onset Alzheimer 病(LOAD)の遺伝的複雑性と臨床的多様性を不十分に表しています。
  • メチレンテトラヒドロ葉酸レダクターゼ(MTHFR)677C>Tバリアントおよびヒ素曝露などの環境要因は、LOAD感受性に関与しています。
  • LOADの臨床前治療開発を進めるためには、改善されたモデルの開発が不可欠です。

研究 の 目的:

  • ヒトLOADリスク対立遺伝子および環境要因を組み込んだ新規マウスモデルを生成および評価すること。
  • これらのモデルがヒトLOAD病理および分子シグネチャの重要な側面を再現する有用性を評価すること。
  • LOADの潜在的なバイオマーカーおよび治療標的を特定すること。

主な方法:

  • ヒト化MTHFR*677C>T、Abeta、APOEe4、およびTrem2*R47H対立遺伝子に対してホモ接合性のLOAD2.Mthfr*677C>Tマウスの生成。
  • 高齢マウスを飲料水中の三酸化ヒ素に曝露し、縦断的な行動、生体測定、およびエンドポイント組織分析(転写、プロテオーム、神経病理)を実施。
  • LC-ICP-MSを用いた尿中種分化によるヒ素解毒の評価。

主要な成果:

  • MTHFR*677C>Tバリアントは、酵素活性の低下と血中ホモシステインレベルの上昇をもたらしました。
  • 高齢のLOAD2.Mthfr*677C>Tマウスは、ヒトADと著しく一致する脳の転写およびプロテオームシグネチャを示しました。
  • ヒ素曝露は、DMAが主要な尿中ヒ素種であるという点で、転写シグネチャとヒトADとの一致をさらに高めました。

結論:

  • Mthfr*677C>Tバリアントおよびヒ素曝露は、ヒトLOADと相関する脳分子プロファイルを変化させます。
  • これらの改変されたマウスモデルは、ヒトLOADの複雑性を捉える上で有用性を示しています。
  • 本研究は、LOADバイオマーカーおよび治療標的の発見のためにこれらのモデルを使用することを支持します。