Abstract
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.
Highlights
The fragile elderly population is the main socio-economic concern of society and it is expected that by 2050 there will be 1.6 billion people over the age of 65 worldwide [1]
A study by Oddo et al suggested that clearance of Aβ42 reduced tau aggregation but increasing the expression of tau had no effect on Aβ42 pathology, suggesting that tau acts downstream of Aβ42 [25]
In order to facilitate an intensive understanding of the different pathways and pathogenesis involved in Alzheimer disease (AD), many appropriate disease models have been developed and applied, including mouse, Caenorhabditis elegans and Drosophila melanogaster [27,28,29]
Summary
The fragile elderly population is the main socio-economic concern of society and it is expected that by 2050 there will be 1.6 billion people over the age of 65 worldwide [1]. The process of aging is often accompanied by the occurrence of various diseases which rarely affect younger individuals, such as cardiovascular disease, cancer, and neurodegeneration. Among all the neurodegenerative disorders, Alzheimer disease (AD) is the most common form of dementia, which causes cognitive deficits, memory loss, and behavioral alterations [3]. According to the World Alzheimer Report, about 50 million people worldwide were reported to have dementia in 2018. By 2050, owing to the increase in the elderly population, this number is expected to increase to 152 million, which is three times what it is now. The pathological mechanism of AD is still elusive, and no therapeutics are available for the prevention or mitigation of the disease progression
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