Nejvíce citovaný článek - PubMed ID 30101709
Insights into the Drug Repositioning Applied to the Alzheimer's Disease Treatment and Future Perspectives
Alzheimer's disease (AD) is a neurodegenerative disease that is usually accompanied by aging, increasingly being the most common cause of dementia in the elderly. This disorder is characterized by the accumulation of beta amyloid plaques (Aβ) resulting from impaired amyloid precursor protein (APP) metabolism, together with the formation of neurofibrillary tangles and tau protein hyperphosphorylation. The exacerbated production of reactive oxygen species (ROS) triggers the process called oxidative stress, which increases neuronal cell abnormalities, most often followed by apoptosis, leading to cognitive dysfunction and dementia. In this context, the development of new therapies for the AD treatment is necessary. Antioxidants, for instance, are promising species for prevention and treatment because they are capable of disrupting the radical chain reaction, reducing the production of ROS. These species have also proven to be adjunctive to conventional treatments making them more effective. In this sense, several recently published works have focused their attention on oxidative stress and antioxidant species. Therefore, this review seeks to show the most relevant findings of these studies.
- Klíčová slova
- Alzheimer’s disease, antioxidants, cellular respiration, free radicals, oxidative stress,
- MeSH
- Alzheimerova nemoc farmakoterapie metabolismus MeSH
- amyloidní beta-protein chemie metabolismus MeSH
- antioxidancia farmakologie terapeutické užití MeSH
- fosforylace MeSH
- klinické zkoušky jako téma MeSH
- lidé MeSH
- oxidační stres účinky léků MeSH
- proteiny tau chemie metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- amyloidní beta-protein MeSH
- antioxidancia MeSH
- proteiny tau MeSH
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.
- Klíčová slova
- chelating agents, drug development, metallodrugs,
- MeSH
- amyloid chemie metabolismus MeSH
- amyloidní beta-protein chemie metabolismus MeSH
- chelátory chemie farmakologie terapeutické užití MeSH
- kovy chemie metabolismus MeSH
- lidé MeSH
- neurodegenerativní nemoci farmakoterapie etiologie metabolismus patologie MeSH
- přehodnocení terapeutických indikací léčivého přípravku MeSH
- simulace molekulární dynamiky MeSH
- simulace molekulového dockingu MeSH
- vyvíjení léků * MeSH
- vztahy mezi strukturou a aktivitou MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- amyloid MeSH
- amyloidní beta-protein MeSH
- chelátory MeSH
- kovy MeSH