Alzheimer\'s disease (AD) has become the fourth leading cause of death in the world. Due to its complex pathogenesis, there is still a lack of effective drug treatments. Studies have found that the metal dyshomeostasis is closely related to other pathogeneses of AD such as oxidative stress, β-amyloid protein deposits, etc. Therefore, it becomes an important target to find the appropriate metal chelating agents to regulate the metal homeostasis. At the same time, because of the complex pathogenesis, single target drugs cannot achieve good effects. Therefore, current studies are mainly focused on exploring multi-target therapy for AD. In this work, the multi-target studies based on metal chelators and other targets with synergistic anti-AD activities were reviewed. The structural characteristics of different chelating agents were summarized and the structure-activity relationship was analyzed, which provided some valuable clues for the subsequent development of anti-AD multi-target drugs based on metal chelating agents.

Drosophila melanogaster has been for over a century the model of choice of several neurobiologists to decipher the formation and development of the nervous system as well as to mirror the pathophysiological conditions of many human neurodegenerative diseases. The rare disease Friedreich’s ataxia (FRDA) is not an exception. Since the isolation of the responsible gene more than two decades ago, the analysis of the fly orthologue has proven to be an excellent avenue to understand the development and progression of the disease, to unravel pivotal mechanisms underpinning the pathology and to identify genes and molecules that might well be either disease biomarkers or promising targets for therapeutic interventions. In this review, we aim to summarize the collection of findings provided by the Drosophila models but also to go one step beyond and propose the implications of these discoveries for the study and cure of this disorder. We will present the physiological, cellular and molecular phenotypes described in the fly, highlighting those that have given insight into the pathology and we will show how the ability of Drosophila to perform genetic and pharmacological screens has provided valuable information that is not easily within reach of other cellular or mammalian models.