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Aging-induced Akt activation involves in aging-related pathologies and Aβ-induced toxicity
Yu-Ru Chen1, Yu-Hsuan Li1, Tsung-Chi Hsieh2
1Department of Pharmacology, National Cheng-Kung University, Tainan, Taiwan.
Aging Cell
|June 12, 2019
Summary
The study reveals that the Akt pathway regulates aging and Alzheimer's disease (AD) pathogenesis. Manipulating Akt activity in fruit flies improved neuronal function and behavior in aged and AD models.
Area of Science:
- Neuroscience
- Genetics
- Molecular Biology
Background:
- Aging and Alzheimer's disease (AD) share altered multicellular signaling and functional changes.
- A common regulator for aging and AD pathogenesis remains unidentified.
Purpose of the Study:
- To investigate the regulatory role of Akt in aging and AD pathogenesis.
- To explore Akt's involvement in cellular and behavioral changes associated with aging and AD.
Main Methods:
- Utilized the fruit fly (Drosophila melanogaster) as an in vivo model.
- Employed genetics and behavioral approaches to study Akt activity.
- Assessed cell survival, locomotor activity, starvation resistance, and learning deficits.
Main Results:
- Akt activity was upregulated during aging via epidermal growth factor receptor activation.
- Downregulating Akt in neurons improved survival and activity in aged and Aβ42 flies.
- Increased cAMP levels mitigated Akt-induced death and Aβ42-induced learning deficits.
- Akt overexpression promoted Notch cleavage, indicating regulation of γ-secretase activity.
Conclusions:
- Akt plays a crucial role in both the aging process and Alzheimer's disease pathology.
- Modulating Akt activity offers a potential therapeutic strategy to restore neuronal function and improve behavior in aging and AD.
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