Abstract
The brain has a unique biological complexity and is responsible for important functions in the human body, such as the command of cognitive and motor functions. Disruptive disorders that affect this organ, e.g., neurodegenerative diseases (NDDs), can lead to permanent damage, impairing the patients’ quality of life and even causing death. In spite of their clinical diversity, these NDDs share common characteristics, such as the accumulation of specific proteins in the cells, the compromise of the metal ion homeostasis in the brain, among others. Despite considerable advances in understanding the mechanisms of these diseases and advances in the development of treatments, these disorders remain uncured. Considering the diversity of mechanisms that act in NDDs, a wide range of compounds have been developed to act by different means. Thus, promising compounds with contrasting properties, such as chelating agents and metal-based drugs have been proposed to act on different molecular targets as well as to contribute to the same goal, which is the treatment of NDDs. This review seeks to discuss the different roles and recent developments of metal-based drugs, such as metal complexes and metal chelating agents as a proposal for the treatment of NDDs.
Highlights
Neurodegenerative diseases (NDDs) are characterized by progressive dysfunction and loss of neurons, which leads to distinct involvement of functional systems defining clinical presentation [1,2,3]
Among the pathologies that belong to this class, it can be highlighted Alzheimer’s disease (AD), which is the most common cause of dementia, along with frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), dementia with Lewy bodies (DLB), Parkinson’s disease (PD), Huntington’s disease (HD), Friedreich’s ataxia (FRDA) and prion disease [4,5]
Lithium-based treatment has been linked to neuroprotection against neurodegenerative frames, for instance, those observed in PD, AD, and HD as well as ALS [78]
Summary
Neurodegenerative diseases (NDDs) are characterized by progressive dysfunction and loss of neurons, which leads to distinct involvement of functional systems defining clinical presentation [1,2,3]. In addition to chelating drugs, it can be highlighted other new approaches to NDDs drug design, such as the development of multifunctional molecules, able to simultaneously combat several pathological features [12] These compounds, including natural products, are able to play many roles, acting as chelating agents, antioxidants, anti-inflammatory drugs, peptide-aggregation reducers and AChE inhibitors, among others [18,19,20,21,22,23,24,25]. The characteristic course of the disease has an average duration of 10–15 years, regarding the onset of clinical symptoms, but presenting a significant variability amongst individuals [10,11]
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