Rac1 and Akt Exhibit Distinct Roles in Mediating Aβ-Induced Memory Damage and Learning Impairment

Kuan Chung Cheng, Ying Hao Chen, Chia Lin Wu, Wang Pao Lee, Chun Hei Antonio Cheung, Hsueh Cheng Chiang

研究成果: Article同行評審

4 引文 斯高帕斯(Scopus)


Accumulated beta-amyloid (Aβ) in the brain is the hallmark of Alzheimer’s disease (AD). Despite Aβ accumulation is known to trigger cellular dysfunctions and learning and memory damage, the detailed molecular mechanism remains elusive. Recent studies have shown that the onset of memory impairment and learning damage in the AD animal is different, suggesting that the underlying mechanism of the development of memory impairment and learning damage may not be the same. In the current study, with the use of Aβ42 transgenic flies as models, we found that Aβ induces memory damage and learning impairment via differential molecular signaling pathways. In early stage, Aβ activates both Ras and PI3K to regulate Rac1 activity, which affects mostly on memory performance. In later stage, PI3K-Akt is strongly activated by Aβ, which leads to learning damage. Moreover, reduced Akt, but not Rac1, activity promotes cell viability in the Aβ42 transgenic flies, indicating that Akt and Rac1 exhibit differential roles in Aβ regulating toxicity. Taken together, different molecular and cellular mechanisms are involved in Aβ-induced learning damage and memory decline; thus, caution should be taken during the development of therapeutic intervention in the future.

頁(從 - 到)5224-5238
期刊Molecular Neurobiology
出版狀態Published - 2021 10月

All Science Journal Classification (ASJC) codes

  • 神經內科
  • 細胞與分子神經科學


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