老化為生理上的不可逆的退化和失能的過程，同時也為阿茲海默症最主要的危險因子。由於全世界在照顧阿茲海默症患者的成本增加，因此對老化的研究及相關藥物治療投入也隨著增加。儘管如此，現今對老化相關的詳細分子機制依然是未解的謎。
本研究使用果蠅作為研究的動物模型，發現AKT蛋白活性在年老的果蠅中有明顯的增加的現象。在果蠅腦中表達AKT蛋白發現會使果蠅壽命縮短，並讓學習能力明顯降低。相反的，減少腦中AKT蛋白可以挽回因老化所造成學習衰退並且提高在飢餓環境下的生存能力。由先前文獻可以得知Aβ42為阿茲海默症主要的致病因子，我們使用藥物抑制AKT活性發現同樣可以延緩因Aβ42所造成的早死和學習損害的症狀；而AKT主要藉由下游蛋白FOXO逆轉因Aβ42所造成的早死和學習能力受損症狀。
另外，Aβ42為β-secretases 及γ- secretases分離amyloid beta-protein precursor所產生的。本研究發現 AKT活性與γ-secretases 活性呈正相關。這項發現透露AKT可藉由調控γ-secretases活性做為未來治療阿茲海默症的方法之一。
另外先前文獻指出cAMP 為主要調控學習記憶的形成。本研究中發現AKT與學習過程有直接相關性。當減少AKT在腦中表現可以挽回因cAMP 失調所造成的學習力受損；同樣的增加cAMP濃度時可以挽回因過度表現AKT所造成的學習受損。本篇研究發現AKT在學習形成過程中主要扮演負調節者的角色。
總結，此篇研究不僅指出AKT在老化及阿茲海默症病程扮演重要角色。此外，也發現AKT也參與學習記憶的過程中，在學習過程中主要扮演負調控的角色。

Aging is considered as an irreversible process resulting in physiological degeneration and dysfunction. It is also the major risking factor of neuron degenerative diseases, such as Alzheimer’s disease (AD). As the cost of social and economic expense on the care of senior people and patient of AD is increased worldwide, there is a growing need to understand and prevent aging process and medicine to treat related impairment. However, the detailed molecular mechanism involved in aging process still remained elusive.
Using Drosophila melanogaster as a model system, we revealed that there is increase of AKT activity in the aging animals. Overexpressed AKT in the brain reduces life-span and jeopardizes the learning ability. Reduced AKT level in the neurons reversed aging-induced learning deficit and prolonged the survival rate in the starvation stress condition. Pharmacological application to inhibit AKT activity improved not only life-span shortening but also learning ability injured in the AD animal. Our data further suggested FOXO is the major downstream protein of AKT signaling to improve the life-span and reverse the learning deficit in the AD animal.
The classic neuropathological signs of Alzheimer’s disease are amyloid plaques. β-amyloid42 (Aβ42) is produced by the sequential action of β and γ-secretases on amyloid beta-protein precursor (APP) . Here, we found AKT activity is correlated with γ-secretases activity. It indicates that AKT plays an critical in AD progress.
Moreover, the previous studies showed that cAMP is major a signal regulator in associative learning process. Our result demonstrated that AKT is activated during learning. Reduced AKT on MB can reverse learning deficit by disruption level of cAMP; increase cAMP level can reverse AKT induced-learning deficit. This study explored AKT is a negative regulator in learning process.
Altogether, our data demonstrate that AKT plays a crucial role in mediating aging-related impairments and AD pathogenesis, which suggest that there is a common molecular mechanism involved in aging process and AD. Moreover, we also discovered AKT is involved in learning process and inhibition of learning ability. It indicated that AKT is as a native regulator in learning process.

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