EVALUATION OF THE RELATIONSHIP BETWEEN AGE AND ACTIVATION OF PROTEIN KINASE RNA-LIKE ER KINASE (PERK) IN A TRANSGENIC MODEL OF ALZHEIMER DISEASE

Ghaffari, M and Sanadgol, N and Maleki, P and Haddadi, M (2021) EVALUATION OF THE RELATIONSHIP BETWEEN AGE AND ACTIVATION OF PROTEIN KINASE RNA-LIKE ER KINASE (PERK) IN A TRANSGENIC MODEL OF ALZHEIMER DISEASE. Studies in Medical Sciences, 32 (8). pp. 607-618.

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Abstract

Alzheimer’s disease (AD) is the main form of dementia and neurodegenerative disorder among the elderly. In this study, we evaluated the activation of protein kinase RNA-like ER kinase (PERK) by monitoring the expression patterns of activating transcription factor 4 (ATF4) during aging in a transgenic Alzheimer's model. Materials & Methods: The human beta-amyloid (hAβ42) mutant gene was expressed in Drosophila by GAL4/UAS system and male flies with UAS-Aβ42 were mated with elav-GAL4 or Ok107-GAL4 female to model AD. The model was confirmed by assessment of performance learning index (PLI) of larvae from first-generation (Ok107) and adult fly’s eyes structure (elav). The expression of ATF4 was evaluated on the 10th, 20th, and 30th days by real-time PCR. Results: The AD model was confirmed by decreasing PLI of larvae (p < 0.05) and degeneration of fly’s eyes structure (p < 0.01). We declined the activity of the GAL4-UAS system by temperature reduction (18 °C) in the first 10 days to decrease neurotoxicity and expression of hAβ42 (p < 0.05) and have the relevant model with maximum toxicity in the adult brain. Expression of ATF4 was similarly upregulated (p < 0.01) in both ages (20 and 30) of the model flies compared to the control group. Conclusion: Given that hAβ42-induced over-expression of ATF4 is the same in different age periods and because PERK signaling is the main source of ATF4 expression, we could conclude that aging is unable to influence the activation of PERK signaling in our model. Further complimentary molecular studies will warrant the possible effects of aging in the activation of other unfolded protein response (IRE1 and ATF6) pathways during AD.

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