INTRODUCTION: Corticobasal syndrome (CBS) is a specific clinical manifestation shared by multiple pathologies. The exact mechanism of this phenomenon remains unclear. Differential diagnosis of CBS in everyday clinical practice is challenging, as this syndrome can overlap with other entities, especially progressive supranuclear palsy Richardson-Steele phenotype (PSP-RS). Several papers have suggested a possible role of vascular pathology as a linking factor in the pathogenesis of CBS based on different neuropathologies. This paper analyses differences in the occurrence of the most common vascular risk factors such as hypertension and lipid profile with respect to dietary habits among patients who fulfill the diagnostic criteria for probable/possible CBS and PSP-RS. MATERIAL AND METHODS: Seventy (70) patients in total were included in the study. Exclusion criteria comprised hydrocephalus, stroke in the past, the presence of marked vascular changes in white matter defined as the presence of vascular change ≥ 1 mm in 3T MRI, medical history of hyperlipidemia or the use of drugs that could impact upon lipid metabolism before the initiation of the neurodegenerative disease, and neoplastic focuses in the central nervous system. Patients with diabetes, or with BMI exceeding 18-25, or who were smokers, or who were affected by chronic stress were also excluded. Data was analysed statistically using the Shapiro-Wilk test, the U Mann-Whitney test for group comparison, and a Bonferroni correction to control the false discovery rate (FDR). RESULTS: Our obtained results indicated a statistically significantly higher level of total cholesterol in the CBS group (p = 0.0039) without a correlation with dietary habits. CONCLUSIONS AND CLINICAL IMPLICATIONS: The results obtained in our study may suggest a possible role of vascular pathology in CBS development. This issue requires further research.
Multiple sclerosis (MS) is a highly disabling, progressive neurodegenerative disease with no curative treatment available. Although significant progress has been made in understanding how MS develops, there remain aspects of disease pathogenesis that are yet to be fully elucidated. In this regard, studies have shown that dysfunctional adenosinergic signaling plays a pivotal role, as patients with MS have altered levels adenosine (ADO), adenosine receptors and proteins involved in the generation and termination of ADO signaling, such as CD39 and adenosine deaminase (ADA). We have therefore performed a literature review regarding the involvement of the adenosinergic system in the development of MS and propose mechanisms by which the modulation of this system can support drug development and repurposing.
- MeSH
- adenosin imunologie MeSH
- adenosindeaminasa imunologie MeSH
- apyrasa imunologie MeSH
- lidé MeSH
- neurodegenerativní nemoci * etiologie imunologie terapie MeSH
- purinergní receptory P1 * imunologie MeSH
- roztroušená skleróza * etiologie imunologie terapie MeSH
- signální transdukce MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
OBJECTIVE: This study was undertaken to follow up predictive factors for α-synuclein-related neurodegenerative diseases in a multicenter cohort of idiopathic/isolated rapid eye movement sleep behavior disorder (iRBD). METHODS: Patients with iRBD from 12 centers underwent a detailed assessment for potential environmental and lifestyle risk factors via a standardized questionnaire at baseline. Patients were then prospectively followed and received assessments for parkinsonism or dementia during follow-up. The cumulative incidence of parkinsonism or dementia was estimated with competing risk analysis. Cox regression analyses were used to evaluate the predictive value of environmental/lifestyle factors over a follow-up period of 11 years, adjusting for age, sex, and center. RESULTS: Of 319 patients who were free of parkinsonism or dementia, 281 provided follow-up information. After a mean follow-up of 5.8 years, 130 (46.3%) patients developed neurodegenerative disease. The overall phenoconversion rate was 24.2% after 3 years, 44.8% after 6 years, and 67.5% after 10 years. Patients with older age (adjusted hazard ratio [aHR] = 1.05) and nitrate derivative use (aHR = 2.18) were more likely to phenoconvert, whereas prior pesticide exposure (aHR = 0.21-0.64), rural living (aHR = 0.53), lipid-lowering medication use (aHR = 0.59), and respiratory medication use (aHR = 0.36) were associated with lower phenoconversion risk. Risk factors for those converting to primary dementia and parkinsonism were generally similar, with dementia-first converters having lower coffee intake and beta-blocker intake, and higher occurrence of family history of dementia. INTERPRETATION: Our findings elucidate the predictive values of environmental factors and comorbid conditions in identifying RBD patients at higher risk of phenoconversion. ANN NEUROL 2022;91:404-416.
- MeSH
- demence epidemiologie etiologie MeSH
- incidence MeSH
- lidé středního věku MeSH
- lidé MeSH
- následné studie MeSH
- neurodegenerativní nemoci epidemiologie etiologie MeSH
- porucha chování v REM spánku komplikace MeSH
- progrese nemoci MeSH
- průzkumy a dotazníky MeSH
- rizikové faktory MeSH
- senioři MeSH
- životní styl MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Adiponektin hraje důležitou roli v regulaci metabolismu glukózy a lipidů, zvyšuje citlivost na inzulin, potlačuje chronický zánět nízkého stupně, apoptózu, oxidační stres a aterosklerotické procesy. Nedávno však byly publikovány studie, které popisují spíše zvýšené hladiny cirkulujícího adiponektinu u pacientů s některými metabolickými, kardiovaskulárními a neurologickými onemocněními. Dokonce vysoké hladiny adiponektinu asociovaly s vyšší mírou úmrtnosti u těchto onemocnění. Situace, kdy se vyšší hladiny adiponektinu nepromítají do lepší inzulinové senzitivity, případně do dalších zdravotních přínosů, je označována jako „paradox adiponektinu“. Cílem tohoto článku je na základě nejnovějších poznatků ukázat možná vysvětlení tohoto jevu.
Adiponectin plays an important role in the regulation of glucose and lipid metabolism, increases insulin sensitivity, and suppresses low-grade chronic inflammation, apoptosis, oxidative stress, and atherosclerotic processes. However, studies have recently been published that describe rather elevated levels of circulating adiponectin in patients with some metabolic, cardiovascular, and neurological diseases. High levels of adiponectin were even associated with a higher mortality rate in these diseases. The situation in which higher levels of adiponectin do not translate into better insulin sensitivity or other health benefits is referred to as the „adiponectin paradox“. The aim of this article is to show possible explanations for this phenomenon based on the latest findings.
- MeSH
- adiponektin * agonisté farmakologie fyziologie škodlivé účinky MeSH
- inzulinová rezistence MeSH
- kardiovaskulární nemoci etiologie patofyziologie MeSH
- lidé MeSH
- metabolické nemoci etiologie patofyziologie MeSH
- neurodegenerativní nemoci etiologie patofyziologie MeSH
- rizikové faktory MeSH
- signální transdukce fyziologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
V současné době není příliš pochybností o tom, že mozkové poranění jakékoli tíže může zanechávat trvalé změny v nervové tkáni a mozkové funkce v různém stupni trvale poškozovat. Mnoho nevyřešených otázek ale zůstává nad vztahem mezi mozkovým poraněním a vývojem chronicky progresivní neurodegenerace. S opakovaným lehkým poraněním mozku bývá nejvíce spojována chronická traumatická encefalopatie. Jedná se ale o neuropatologicky definovanou jednotku, jejíž neurobiologický i klinický význam spolehlivě ukáže až budoucnost. Na základě epidemiologických studií lze přesto konstatovat, že anamnéza mozkového poranění souvisí v dalším průběhu života se zvýšeným rizikem klinické diagnózy různých neurodegenerativních onemocnění. Zdá se přitom, že TBI výrazněji nevyčnívá nad ostatní ovlivnitelné rizikové faktory. Tento přehled si klade za cíl popsat současný stav na tomto poli neurověd.
There now is little doubt that traumatic brain injuries of any severity can leave permanent changes in neural tissue and lead to long-term brain damage. However, many questions remain over the relationship between brain injury and the development of a chronic progressive neurodegenerative process. Chronic traumatic encephalopathy is most commonly associated with repeated mild brain injury, but this is a neuropathologically defined concept whose neurobiological and clinical significance remains to be elucidated. Nevertheless, epidemiological studies suggest that a history of brain injury is associated with an increased risk of clinical diagnosis of various neurodegenerative diseases later in life. At the same time, TBI does not seem to stand out significantly above other modifiable risk factors. This review aims to describe the current state of this field of neuroscience.
- MeSH
- chronická traumatická encefalopatie patologie MeSH
- lidé MeSH
- neurodegenerativní nemoci * etiologie MeSH
- traumatické poranění mozku * komplikace MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Numerous pathological changes of subcellular structures are characteristic hallmarks of neurodegeneration. The main research has focused to mitochondria, endoplasmic reticulum, Golgi apparatus, lysosomal networks as well as microtubular system of the cell. The sequence of specific organelle damage during pathogenesis has not been answered yet. Exposition to rotenone is used for simulation of neurodegenerative changes in SH-SY5Y cells, which are widely used for in vitro modelling of Parkinson ́s disease pathogenesis. Intracellular effects were investigated in time points from 0 to 24 h by confocal microscopy and biochemical analyses. Analysis of fluorescent images identified the sensitivity of organelles towards rotenone in this order: microtubular cytoskeleton, mitochondrial network, endoplasmic reticulum, Golgi apparatus and lysosomal network. All observed morphological changes of intracellular compartments were identified before alphaS protein accumulation. Therefore, their potential as an early diagnostic marker is of interest. Understanding of subcellular sensitivity in initial stages of neurodegeneration is crucial for designing new approaches and a management of neurodegenerative disorders.
- MeSH
- apoptóza MeSH
- insekticidy toxicita MeSH
- lidé MeSH
- mikrotubuly účinky léků metabolismus patologie MeSH
- mitochondrie účinky léků metabolismus patologie MeSH
- nádorové buněčné linie MeSH
- NADPH-oxidasy metabolismus MeSH
- neuroblastom komplikace MeSH
- neurodegenerativní nemoci etiologie metabolismus patologie MeSH
- rotenon toxicita MeSH
- viabilita buněk MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Glaucoma, one of the most common causes of blindness in developing countries today, involves a progressive loss of neural cells in the optic nerve that leads to progressive, irreversible vision loss. Increased intraocular pressure (IOP) presents as a major risk factor for glaucoma, although there exist cases of glaucoma patients with normal IOP that exhibit damage to retinal ganglion cells (RGCs) and the optic nerve. However, treatment approaches have maintained their focus on modifying IOP due to a lack of other modifiable risks factors. Traditional concepts in glaucoma involve the neuronal environment and external effects as a source of causative factors; however, studies have yet to investigate whether the molecular profile of RGCs in glaucoma patients makes them more vulnerable and/or susceptible to external damage. Our hypothesis states that molecular changes at the whole cell, gene expression, and electrophysiological level of the neurons can contribute to their degeneration. Herein, we briefly describe different types of glaucoma and any similarities to different molecular and cellular features of neurodegeneration. To test our hypothesis, we describe human induced pluripotent stem cells (hiPSCs) as a reliable cellular tool to model neurodegenerative aspects of glaucoma to reveal the multiple pathological molecular mechanisms underlying disease development.
- MeSH
- genetická predispozice k nemoci * MeSH
- glaukom * etiologie genetika metabolismus patologie MeSH
- indukované pluripotentní kmenové buňky * MeSH
- lidé MeSH
- neurodegenerativní nemoci * etiologie genetika metabolismus patologie MeSH
- retinální gangliové buňky * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Research Support, N.I.H., Extramural MeSH
- Research Support, U.S. Gov't, Non-P.H.S. MeSH
According to the United States Centers for Disease Control and Prevention (CDC), as of July 11, 2016, the reported average incidence of children diagnosed with an autism spectrum disorder (ASD) was 1 in 68 (1.46%) among 8-year-old children born in 2004 and living within the 11 monitoring sites' surveillance areas in the United States of America (USA) in 2012. ASD is a multifaceted neurodevelopmental disorder that is also considered a hidden disability, as, for the most part; there are no apparent morphological differences between children with ASD and typically developing children. ASD is diagnosed based upon a triad of features including impairment in socialization, impairment in language, and repetitive and stereotypic behaviors. The increasing incidence of ASD in the pediatric population and the lack of successful curative therapies make ASD one of the most challenging disorders for medicine. ASD neurobiology is thought to be associated with oxidative stress, as shown by increased levels of reactive oxygen species and increased lipid peroxidation, as well as an increase in other indicators of oxidative stress. Children with ASD diagnosis are considered more vulnerable to oxidative stress because of their imbalance in intracellular and extracellular glutathione levels and decreased glutathione reserve capacity. Several studies have suggested that the redox imbalance and oxidative stress are integral parts of ASD pathophysiology. As such, early assessment and treatment of antioxidant status may result in a better prognosis as it could decrease the oxidative stress in the brain before it can induce more irreversible brain damage. In this review, many aspects of the role of oxidative stress in ASD are discussed, taking into account that the process of oxidative stress may be a target for therapeutic interventions.
- MeSH
- aerobióza MeSH
- antioxidancia metabolismus MeSH
- centrální nervový systém metabolismus MeSH
- dítě MeSH
- dysbióza komplikace MeSH
- gastrointestinální nemoci komplikace MeSH
- glutathionperoxidasa metabolismus MeSH
- incidence MeSH
- lidé MeSH
- metalothionein metabolismus MeSH
- mitochondrie metabolismus MeSH
- mozek - chemie MeSH
- neurodegenerativní nemoci etiologie metabolismus MeSH
- oxidace-redukce MeSH
- oxidační stres * MeSH
- peroxidace lipidů MeSH
- poruchy autistického spektra epidemiologie imunologie metabolismus patofyziologie MeSH
- předškolní dítě MeSH
- scavengery volných radikálů metabolismus MeSH
- selen fyziologie MeSH
- selenoproteiny metabolismus MeSH
- střevní mikroflóra MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- předškolní dítě MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
