Role of the AKT in the aging process and memory formation

Abstract

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

Date of Award	2017 Aug 2
Original language	English
Supervisor	HsuehCheng Chinag (Supervisor)