Alzheimer´s disease (AD) is a neurodegenerative disorder with no known cure and rapid rise in incidence. The predominant cognitive impairment is currently treated using cognitive enhancers like cholinesterase inhibitors. The two molecular hallmarks of AD are amyloid plaques created from an amyloid precursor protein and hyperphosphorylated tau protein that is deposited as neurofibrillary tangles inside neurons. A number of pathological mechanisms follow or precede these formations. Alteration in mitochondrial function and deposition of heavy metals are reported. The disease progression is enhanced by oxidative stress. However, the role of oxidative stress is not universally accepted. The current review covers and discusses the basic evidence and role of oxidative stress in AD development.

• MeSH
• Alzheimerova nemoc metabolismus   patologie   MeSH
• amyloidní plaky metabolismus   patologie   MeSH
• amyloidový prekurzorový protein beta metabolismus   MeSH
• lidé MeSH
• mitochondrie metabolismus   patologie   MeSH
• neurofibrilární klubka metabolismus   patologie   MeSH
• oxidační stres * MeSH
• proteiny tau metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

Alzheimer's disease (AD) represents a highly common form of dementia, but can be diagnosed in the earlier stages before dementia onset. Early diagnosis is crucial for successful therapeutic intervention. The introduction of new diagnostic biomarkers for AD is aimed at detecting underlying brain pathology. These biomarkers reflect structural or biochemical changes related to AD. Examination of cerebrospinal fluid has many drawbacks; therefore, the search for sensitive and specific blood markers is ongoing. Investigation is mainly focused on upstream processes, among which oxidative stress in the brain is of particular interest. Products of oxidative stress may diffuse into the blood and evaluating them can contribute to diagnosis of AD. However, results of blood oxidative stress markers are not consistent among various studies, as documented in this review. To find a specific biochemical marker for AD, we should concentrate on specific metabolic products formed in the brain. Specific fluorescent intermediates of brain lipid peroxidation may represent such candidates as the composition of brain phospholipids is unique. They are small lipophilic molecules and can diffuse into the blood stream, where they can then be detected. We propose that these fluorescent products are potential candidates for blood biomarkers of AD.

• MeSH
• Alzheimerova nemoc krev   diagnóza   patofyziologie   MeSH
• antioxidancia analýza   MeSH
• biologické markery krev   MeSH
• lidé MeSH
• mozek metabolismus   patofyziologie   MeSH
• nukleové kyseliny metabolismus   MeSH
• oxidační stres * MeSH
• peroxidace lipidů MeSH
• proteiny metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

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.

• 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

• MeSH
• Alzheimerova nemoc etiologie   farmakoterapie   metabolismus   MeSH
• amyloidní beta-protein metabolismus   MeSH
• apolipoproteiny E genetika   metabolismus   MeSH
• cholesterol metabolismus   MeSH
• lidé MeSH
• oxidační stres MeSH
• přehledová literatura jako téma MeSH
• Check Tag
• lidé MeSH

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.

• 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

Alzheimer's disease (AD) is a complex neurodegenerative disorder with major clinical hallmarks of memory loss, dementia, and cognitive impairment. Besides the extensive neuron-oriented research, an increasing body of evidence suggests that glial cells, namely astrocytes, microglia, NG2 glia and oligodendrocytes, may play an important role in the pathogenesis of this disease. In the first part of this review, AD pathophysiology in humans is briefly described and compared with disease progression in routinely used animal models. The relevance of findings obtained in animal models of AD is also discussed with respect to AD pathology in humans. Further, this review summarizes recent findings regarding the role/participation of glial cells in pathogenesis of AD, focusing on changes in their morphology, functions, proteins and gene expression profiles. As for astrocytes and microglia, they are fundamental for the progression and outcome of AD either because they function as effector cells releasing cytokines that play a role in neuroprotection, or because they fail to fulfill their homeostatic functions, ultimately leaving neurons to face excitotoxicity and oxidative stress. Next, we turn our attention towards NG2 glia, a novel and distinct class of glial cells in the central nervous system (CNS), whose role in a variety of human CNS diseases has begun to emerge, and we also consider the participation of oligodendrocytes in the pathogenesis and progression of AD. Since AD is currently an incurable disease, in the last part of our review we hypothesize about possible glia-oriented treatments and provide a perspective of possible future advancements in this field.

• MeSH
• Alzheimerova nemoc farmakoterapie   patologie   patofyziologie   MeSH
• lidé MeSH
• neuroglie účinky léků   patologie   fyziologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

Copper (Cu) is a vital redox dynamic metal that is possibly poisonous in superfluous. Metals can traditionally or intricately cause propagation in reactive oxygen species (ROS) accretion in cells and this may effect in programmed cell death. Accumulation of Cu causes necrosis that looks to be facilitated by DNA damage, followed by activation of P53. Cu dyshomeostasis has also been concerned in neurodegenerative disorders such as Alzheimer, Amyotrophic lateral sclerosis (ALS) or Menkes disease and is directly related to neurodegenerative syndrome that usually produces senile dementia. These mortal syndromes are closely related with an immense damage of neurons and synaptic failure in the brain. This review focuses on copper mediated neurological disorders with insights into amyotrophic lateral sclerosis, Alzheimer and Menkes disease.

• MeSH
• Alzheimerova nemoc etiologie   patologie   MeSH
• amyotrofická laterální skleróza etiologie   patologie   MeSH
• lidé MeSH
• měď škodlivé účinky   MeSH
• Menkesova choroba etiologie   patologie   MeSH
• mozek metabolismus   patologie   MeSH
• oxidační stres MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

Age related neurodegenerative disorders are becoming a serious public health problem. Alzheimer's disease (AD) is a progressive disease pathologically recognizable by deposition of neurofibrillary tangles and amyloid plaques. Oxidative stress probably plays a pivotal role in AD, but despite expectations, antioxidants such as vitamin E, vitamin C, beta carotene, and flavonoids have failed as effective prophylaxis and/or treatment. Melatonin, a hormone controlling circadian rhythm, is a potent terminal antioxidant. In vitro tests and animal models have established that the application of melatonin could be beneficial for the amelioration of AD progression. Unfortunately, melatonin effects in human beings are not well understood and a lot of work has still to be done. The review summarizes the basic facts about melatonin and its prospects as a treatment for AD using its hormonal and antioxidant properties.

• MeSH
• Alzheimerova nemoc etiologie   farmakoterapie   patologie   MeSH
• amyloidní beta-protein izolace a purifikace   metabolismus   škodlivé účinky   MeSH
• amyloidní plaky diagnóza   etiologie   patofyziologie   MeSH
• amyloidóza diagnóza   patofyziologie   patologie   MeSH
• antioxidancia terapeutické užití   MeSH
• financování organizované MeSH
• lidé MeSH
• melatonin analogy a deriváty   terapeutické užití   MeSH
• metaanalýza jako téma MeSH
• neurodegenerativní nemoci etiologie   patofyziologie   patologie   MeSH
• neurofibrilární klubka genetika   imunologie   účinky léků   MeSH
• oxidační stres genetika   imunologie   MeSH
• proteiny tau izolace a purifikace   metabolismus   škodlivé účinky   MeSH
• teoretické modely MeSH
• věkové faktory MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• přehledy MeSH

Rezistence tkání na působení inzulinu se účastní etiopatogeneze diabetu mellitu 2. typu a je také spojena se zvýšenou kardiovaskulární morbiditou i mortalitou. K hlavním patogenetickým mechanismům, které se v působení inzulinové rezistence u těchto onemocnění uplatňují, patří oxidační stres a subklinický zánětlivý proces. V posledních letech bylo zjištěno, že inzulinová rezistence v periferních tkáních i v mozku hraje zřejmě roli také v patogenezi některých neurologických a psychiatrických onemocnění, zejména sporadické formy Alzheimerovy demence, depresivních poruch a schizofrenie, které jsou charakterizovány zvýšeným výskytem diabetu mellitu 2. typu i kardiovaskulárních onemocnění. Inzulinová rezistence a metabolické poruchy s ní spojené zasahují do rozvoje atrofie specifických oblastí v mozku (např. hipokampu), souvisí s tvorbou amyloidových plaků, patologických intraneuronálních klubek i s poruchou struktur zodpovídajících za schopnost paměti a učení. V článku jsou shrnuty mechanismy, kterými se inzulinová rezistence uplatňuje v patogenezi vybraných neuropsychiatrických onemocnění.

Tissue resistance to the insulin effects is taking part in the etiopathogenesis of diabetes mellitus type 2; moreover, it is linked with increased cardiovascular morbitidy and mortality. The principal pathogenetic mechanisms of insulin resistance playing a role in these diseases include oxidative stress and subclinical inflammatory processes. The findings of the last years revealed the role of peripheral as well as brain insulin resistance in the pathogenesis of some neurological and psychiatrical diseases, particularly the sporadic form of Alzheimer disease, depressive disorders and schizophrenia, all of them being characterized with increased prevalence of diabetes mellitus type 2 and/or cardivascular disease. Insulin resistance and associated metabolic disturbances interfere with the development of specific brain areas (e. g. hippocampus), are linked with the formation of amyloid plaques, pathologic intraneuronal tangles, and also with the deterioration of the structures responsible for memory and learning processes. The paper reviews the mechanisms, by which insulin resistance influences the pathogenesis of selected neuropsychiatric disorders.

• Klíčová slova
• subklinický zánět, Alzheimerova choroba, neurodegenerativní onemocnění,
• MeSH
• Alzheimerova nemoc patofyziologie   MeSH
• bipolární porucha metabolismus   patofyziologie   MeSH
• deprese MeSH
• depresivní poruchy metabolismus   patofyziologie   MeSH
• diabetes mellitus 2. typu farmakoterapie   komplikace   MeSH
• financování organizované MeSH
• Huntingtonova nemoc genetika   patofyziologie   MeSH
• inzulinová rezistence MeSH
• lidé MeSH
• metabolický syndrom komplikace   MeSH
• oxidační stres MeSH
• Parkinsonova nemoc metabolismus   patofyziologie   MeSH
• schizofrenie metabolismus   patofyziologie   MeSH
• zánět metabolismus   patofyziologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• přehledy MeSH

Vascular cognitive impairment (VCI) is the second most common cause of cognitive deficit after Alzheimer's disease. Since VCI patients represent an important target population for prevention, an ongoing effort has been made to elucidate the pathogenesis of this disorder. In this review, we summarize the information from animal models on the molecular changes that occur in the brain during a cerebral vascular insult and ultimately lead to cognitive deficits in VCI. Animal models cannot effectively represent the complex clinical picture of VCI in humans. Nonetheless, they allow some understanding of the important molecular mechanisms leading to cognitive deficits. VCI may be caused by various mechanisms and metabolic pathways. The pathological mechanisms, in terms of cognitive deficits, may span from oxidative stress to vascular clearance of toxic waste products (such as amyloid beta) and from neuroinflammation to impaired function of microglia, astrocytes, pericytes, and endothelial cells. Impaired production of elements of the immune response, such as cytokines, and vascular factors, such as insulin-like growth factor 1 (IGF-1), may also affect cognitive functions. No single event could be seen as being the unique cause of cognitive deficits in VCI. These events are interconnected, and may produce cascade effects resulting in cognitive impairment.

• MeSH
• Alzheimerova nemoc metabolismus   MeSH
• amyloidní beta-protein metabolismus   MeSH
• astrocyty metabolismus   MeSH
• cytokiny metabolismus   MeSH
• endoteliální buňky metabolismus   MeSH
• insulinu podobný růstový faktor I metabolismus   MeSH
• kognice * MeSH
• kognitivní dysfunkce metabolismus   patologie   MeSH
• lidé MeSH
• mikroglie metabolismus   MeSH
• modely u zvířat MeSH
• mozek metabolismus   MeSH
• oxid dusnatý MeSH
• oxidační stres MeSH
• pericyty metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH