Pharmacological Treatment of Alzheimer’s Disease: Insights from Drosophila melanogaster

Abstract

<jats:p>Aging is an ineluctable law of life. During the process of aging, the occurrence of neurodegenerative disorders is prevalent in the elderly population and the predominant type of dementia is Alzheimer’s disease (AD). The clinical symptoms of AD include progressive memory loss and impairment of cognitive functions that interfere with daily life activities. The predominant neuropathological features in AD are extracellular β-amyloid (Aβ) plaque deposition and intracellular neurofibrillary tangles (NFTs) of hyperphosphorylated Tau. Because of its complex pathobiology, some tangible treatment can only ameliorate the symptoms, but not prevent the disease altogether. Numerous drugs during pre-clinical or clinical studies have shown no positive effect on the disease outcome. Therefore, understanding the basic pathophysiological mechanism of AD is imperative for the rational design of drugs that can be used to prevent this disease. Drosophila melanogaster has emerged as a highly efficient model system to explore the pathogenesis and treatment of AD. In this review we have summarized recent advancements in the pharmacological research on AD using Drosophila as a model species, discussed feasible treatment strategies and provided further reference for the mechanistic study and treatment of age-related AD.</jats:p>

Iron Metabolism in Aging and Age-Related Diseases

“…Under pathological conditions, APP passes through the neurodegenerative pathway of amyloid. APP can be cut by β-secretase and then cut by γ-secretase to produce Aβ [ 94 ]. The formation of Aβ and its accumulation in the brain can be weakened by stimulating α-secretase.…”

American Ginseng for the Treatment of Alzheimer’s Disease: A Review

“…This model has the advantage, to some extent, of reducing the use of drugs, which in turn reduces the stress of the experiment and increases the selectivity of ginsenosides, but in this study, the drosophila was modeled as Parkinson's disease [154]. Of course, there have been studies using drosophila models to study pharmacological treatments for AD [228], and there have even been studies on the establishment of a drosophila model for AD [229,230], but there have been few studies on the use of ginsenosides to treat AD using a drosophila model, which is a new and innovative direction.…”

The soluble epoxide hydrolase inhibitor TPPU alleviates Aβ-mediated neuroinflammatory responses in Drosophila and cellular models of Alzheimer's disease

“…Drosophila do not have an integrated blood-brain barrier, such as that observed in humans, and drugs can easily enter the Drosophila brain, which makes Drosophila an excellent genetic animal model for studying neurodegenerative diseases. In addition, this model has the advantages of low cost, simple feeding methods, short life cycle, strong reproduction ability, large offspring numbers, and ease of phenotype analysis [41,42]. We used the UAS-GAL4 system to hybridize Aβ42-transgenic Drosophila to investigate the effect of aging on Aβ42-transgenic Drosophila as well as the anti-neuroin ammatory and neuroprotective effects of TPPU.…”