Iron and copper chelation therapy plays a crucial role in treating conditions associated with metal overload, such as hemochromatosis or Wilson's disease. However, conventional chelators face challenges in reaching the core of iron and copper metabolism - the mitochondria. Mitochondria-targeted chelators can specifically target and remove metal ions from mitochondria, showing promise in treating diseases linked to mitochondrial dysfunction, including neurodegenerative diseases and cancer. Additionally, they serve as specific mitochondrial metal sensors. However, designing these new molecules presents its own set of challenges. Depending on the chelator's intended use to prevent or to promote redox cycling of the metals, the chelating moiety must possess different donor atoms and an optimal value of the electrode potential of the chelator-metal complex. Various targeting moieties can be employed for selective delivery into the mitochondria. This review also provides an overview of the current progress in the design of mitochondria-targeted chelators and their biological activity investigation.
- MeSH
- chelátory železa farmakologie MeSH
- chelátory * terapeutické užití metabolismus MeSH
- chelátová terapie metody MeSH
- lidé MeSH
- měď * metabolismus MeSH
- mitochondrie * metabolismus účinky léků MeSH
- železo * metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
INTRODUCTION: Wilson's disease (WD) is a potentially treatable, inherited disorder resulting from impaired copper metabolism. Pathological copper accumulation causes a range of symptoms, most commonly hepatic and a wide spectrum of neurological symptoms including tremor, dystonia, chorea, parkinsonism, dysphagia, dysarthria, gait and posture disturbances. To reduce copper overload, anti-copper drugs are used that improve liver function and neurological symptoms in up to 85% of patients. However, in some WD patients, treatment introduction leads to neurological deterioration, and in others, neurological symptoms persist with no improvement or improvement only after several years of treatment, severely affecting the patient's quality of life. AREAS COVERED: This review appraises the evidence on various pharmacological and non-pharmacological therapies, neurosurgical procedures and liver transplantation for the management of neurological WD symptoms. The authors also discuss the neurological symptoms of WD, causes of deterioration and present symptomatic treatment options. EXPERT OPINION: Based on case and series reports, current recommendations and expert opinion, WD treatment is focused mainly on drugs leading to negative copper body metabolism (chelators or zinc salts) and copper-restricted diet. Treatment of WD neurological symptoms should follow general recommendations of symptomatic treatment. Patients should be always considered individually, especially in the case of severe, disabling neurological symptoms.
- Klíčová slova
- vazače fosfátů,
- MeSH
- chelátory farmakologie terapeutické užití MeSH
- chronické selhání ledvin * komplikace patofyziologie MeSH
- dialýza ledvin metody MeSH
- fibroblastové růstové faktory fyziologie MeSH
- fosfáty antagonisté a inhibitory metabolismus škodlivé účinky MeSH
- fosfor dietní aplikace a dávkování škodlivé účinky MeSH
- hemodiafiltrace metody MeSH
- hyperfosfatemie * etiologie farmakoterapie terapie MeSH
- hyperparatyreóza etiologie komplikace patofyziologie MeSH
- lanthan farmakologie škodlivé účinky terapeutické užití MeSH
- lidé MeSH
- sacharosa analogy a deriváty MeSH
- sevelamer farmakologie škodlivé účinky terapeutické užití MeSH
- sloučeniny hliníku škodlivé účinky MeSH
- sloučeniny vápníku škodlivé účinky terapeutické užití MeSH
- sloučeniny železa farmakologie terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
The presented case demonstrates that acute lead poisoning may occur due to just short-term exposure to a mixture of lead-containing dust and ammunition. Such exposure may result in high blood lead levels persisting for years in the absence of any symptoms. A middle-aged male with a history of an approximately 7-day cleanup of an old recreational firing range with large ammunition and dust deposits presented to an emergency department with abdominal pain, dyspnea, fatigue and impaired cognitive function. Given his occupational history, specific tests were performed that showed high lead concentrations in both blood and urine. The patient was diagnosed with acute lead poisoning. He was started on chelation therapy that improved both clinical and laboratory parameters. Over a subsequent nearly 3-year follow-up, the patient's blood lead levels fluctuated and continued to be increased. Given the absence of other sources of lead exposure, these were likely due to the formation of bone deposits. Med Pr. 2020;71(3):375-9.
- MeSH
- akutní nemoc MeSH
- bolesti břicha chemicky indukované MeSH
- chelátory terapeutické užití MeSH
- lidé středního věku MeSH
- lidé MeSH
- otrava olovem diagnóza farmakoterapie MeSH
- pracoviště MeSH
- pracovní expozice škodlivé účinky MeSH
- střelné zbraně * MeSH
- výsledek terapie MeSH
- znečištění vzduchu ve vnitřním prostředí škodlivé účinky MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
- Geografické názvy
- Polsko 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.
- 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
Wilson disease (WD) is a potentially treatable, inherited disorder of copper metabolism that is characterized by the pathological accumulation of copper. WD is caused by mutations in ATP7B, which encodes a transmembrane copper-transporting ATPase, leading to impaired copper homeostasis and copper overload in the liver, brain and other organs. The clinical course of WD can vary in the type and severity of symptoms, but progressive liver disease is a common feature. Patients can also present with neurological disorders and psychiatric symptoms. WD is diagnosed using diagnostic algorithms that incorporate clinical symptoms and signs, measures of copper metabolism and DNA analysis of ATP7B. Available treatments include chelation therapy and zinc salts, which reverse copper overload by different mechanisms. Additionally, liver transplantation is indicated in selected cases. New agents, such as tetrathiomolybdate salts, are currently being investigated in clinical trials, and genetic therapies are being tested in animal models. With early diagnosis and treatment, the prognosis is good; however, an important issue is diagnosing patients before the onset of serious symptoms. Advances in screening for WD may therefore bring earlier diagnosis and improvements for patients with WD.
- MeSH
- chelátory terapeutické užití MeSH
- hepatolentikulární degenerace diagnóza genetika patofyziologie MeSH
- kvalita života psychologie MeSH
- lidé MeSH
- měď škodlivé účinky metabolismus MeSH
- molybden terapeutické užití MeSH
- potravní doplňky MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Research Support, N.I.H., Extramural MeSH
- MeSH
- chelátory terapeutické užití MeSH
- chronické selhání ledvin komplikace MeSH
- cinakalcet farmakologie terapeutické užití MeSH
- dialýza ledvin MeSH
- hyperfosfatemie patofyziologie MeSH
- hypokalcemie patofyziologie MeSH
- kalcimimetika farmakologie terapeutické užití MeSH
- kalcitriol metabolismus nedostatek MeSH
- minerálová a kostní nemoc při chronickém onemocnění ledvin * diagnóza radiografie MeSH
- nedostatek vitaminu D MeSH
- osteoporóza etiologie farmakoterapie MeSH
- parathormon biosyntéza metabolismus škodlivé účinky MeSH
- paratyreoidektomie MeSH
- resorpce kosti dietoterapie etiologie metabolismus patofyziologie MeSH
- sekundární hyperparatyreóza komplikace MeSH
- sevelamer farmakologie terapeutické užití MeSH
- vitamin D analogy a deriváty aplikace a dávkování MeSH
- Publikační typ
- přehledy MeSH
LEVEL OF EVIDENCE: 5 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2018;47:282-285.
- MeSH
- časové faktory MeSH
- chelátory škodlivé účinky terapeutické užití MeSH
- dospělí MeSH
- hepatolentikulární degenerace diagnostické zobrazování farmakoterapie metabolismus MeSH
- lidé MeSH
- longitudinální studie MeSH
- magnetická rezonanční tomografie MeSH
- měď analýza MeSH
- mladiství MeSH
- mladý dospělý MeSH
- penicilamin škodlivé účinky terapeutické užití MeSH
- počítačové zpracování obrazu MeSH
- šedá hmota diagnostické zobrazování účinky léků MeSH
- studie případů a kontrol MeSH
- tkáňová distribuce MeSH
- ultrasonografie dopplerovská transkraniální MeSH
- železo analýza terapeutické užití MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
- MeSH
- anemie chemicky indukované MeSH
- antidota aplikace a dávkování MeSH
- bolesti břicha chemicky indukované MeSH
- chelátory aplikace a dávkování terapeutické užití MeSH
- diferenciální diagnóza MeSH
- lidé středního věku MeSH
- lidé MeSH
- olovo analýza krev MeSH
- otrava olovem * diagnóza etiologie farmakoterapie MeSH
- zácpa chemicky indukované MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
