Of note, we also observed reduced cell death and a complete rescue of memory deficits when we crossed a null mutation in Drosophila Acer into each transgenic line demonstrating that the target of captopril in Drosophila is Acer. Importantly, neither drug rescued brain cell death in Drosophila expressing human Tau, suggesting that RAS inhibitors specifically target the amyloid pathway. However, neither drug affects production, accumulation or clearance of Aβ 42. Similarly, both drugs reduce cell death in Drosophila expressing human Aβ 42 and losartan significantly rescues memory deficits. Captopril also significantly rescues memory defects in these flies.
We show that captopril, an ACE-I, and losartan, an ARB, can suppress a rough eye phenotype and brain cell death in flies expressing a mutant human C99 transgene. Importantly, while ACE orthologs have been identified in Drosophila, other RAS components are not conserved.
Here, we used a genetic and pharmacological approach to evaluate the beneficial effects of angiotensin converting enzyme inhibitors (ACE-Is) and angiotensin receptor blockers (ARBs) in Drosophila expressing AD-related transgenes. Recently, studies have reported that inhibitors of the mammalian renin angiotensin system (RAS) result in a significant reduction in the incidence and progression of AD by unknown mechanisms. Alzheimer’s disease (AD) is a degenerative disorder that causes progressive memory and cognitive decline.
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