Alzheimer's disease (AD) is a neurodegenerative disorder presenting one of the biggest healthcare challenges in developed countries. No effective treatment exists. In recent years the main focus of AD research has been on the amyloid hypothesis, which postulates that extracellular precipitates of beta amyloid (Aβ) derived from amyloid precursor protein (APP) are responsible for the cognitive impairment seen in AD. Treatment strategies have been to reduce Aβ production through inhibition of enzymes responsible for its formation, or to promote resolution of existing cerebral Aβ plaques. However, these approaches have failed to demonstrate significant cognitive improvements. Intracellular rather than extracellular events may be fundamental in AD pathogenesis. Selenate is a potent inhibitor of tau hyperphosphorylation, a critical step in the formation of neurofibrillary tangles. Some selenium (Se) compounds e.g. selenoprotein P also appear to protect APP against excessive copper and iron deposition. Selenoproteins show anti-inflammatory properties, and protect microtubules in the neuronal cytoskeleton. Optimal function of these selenoenzymes requires higher Se intake than what is common in Europe and also higher intake than traditionally recommended. Supplementary treatment with N-acetylcysteine increases levels of the antioxidative cofactor glutathione and can mediate adjuvant protection. The present review discusses the role of Se in AD treatment and suggests strategies for AD prevention by optimizing selenium intake, in accordance with the metal dysregulation hypothesis. This includes in particular secondary prevention by selenium supplementation to elderly with mild cognitive impairment.

• Klíčová slova
• Alzheimer’s disease, Copper, Iron, Neuroinflammation, Selenium, Transmitters,
• MeSH
• Alzheimerova nemoc dietoterapie   farmakoterapie   metabolismus   MeSH
• lidé MeSH
• oxidační stres účinky léků   MeSH
• potravní doplňky * MeSH
• sloučeniny selenu aplikace a dávkování   metabolismus   farmakologie   terapeutické užití   MeSH
• zánět farmakoterapie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• sloučeniny selenu MeSH

Alzheimer's disease (AD) is a debilitating progressive neurodegenerative disorder that ultimately leads to the patient's death. Despite the fact that novel pharmacological approaches endeavoring to block the neurodegenerative process are still emerging, none of them have reached use in clinical practice yet. Thus, palliative treatment represented by acetylcholinesterase inhibitors (AChEIs) and memantine are still the only therapeutics used. Following the multi-target directed ligands (MTDLs) strategy, herein we describe the synthesis, biological evaluation and docking studies for novel 7-methoxytacrine-p-anisidine hybrids designed to purposely target both cholinesterases and the amyloid cascade. Indeed, the novel derivatives proved to be effective non-specific cholinesterase inhibitors showing non-competitive AChE inhibition patterns. This compounds' behavior was confirmed in the subsequent molecular modeling studies.

• Klíčová slova
• 7-methoxy-tacrine, Alzheimer’s disease, MTDLs, acetylcholinesterase, butyrylcholinesterase, tacrine,
• MeSH
• acetylcholinesterasa chemie   MeSH
• amyloidní beta-protein antagonisté a inhibitory   chemie   MeSH
• aniliny chemická syntéza   chemie   MeSH
• cholinesterasové inhibitory chemická syntéza   chemie   MeSH
• kinetika MeSH
• látky ovlivňující centrální nervový systém chemická syntéza   chemie   MeSH
• lidé MeSH
• rekombinantní proteiny chemie   MeSH
• simulace molekulového dockingu MeSH
• takrin analogy a deriváty   MeSH
• vazebná místa MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• acetylcholinesterasa MeSH
• amyloidní beta-protein MeSH
• aniliny MeSH
• cholinesterasové inhibitory MeSH
• látky ovlivňující centrální nervový systém MeSH
• rekombinantní proteiny MeSH
• takrin MeSH