The cellular quality control system degrades abnormal or misfolded proteins and consists of three different mechanisms: the ubiquitin proteasomal system (UPS), autophagy and molecular chaperones. Any ...disturbance in this system causes proteins to accumulate, resulting in neurodegenerative diseases such as amyotrophic lateral sclerosis, Alzheimer's disease (AD), Parkinson's disease, Huntington's disease and prion or polyglutamine diseases. Alzheimer's disease is currently one of the most common age‐related neurodegenerative diseases. However, its exact cause and pathogenesis are unknown. Currently approved medications for AD provide symptomatic relief; however, they fail to influence disease progression. Moreover, the components of the cellular quality control system represent an important focus for the development of targeted and potent therapies for managing AD. This review aims to evaluate whether existing evidence supports the hypothesis that UPS impairment causes the early pathogenesis of neurodegenerative disorders. The first part presents basic information about the UPS and its molecular components. The next part explains how the UPS is involved in neurodegenerative disorders. Finally, we emphasize how the UPS influences the management of AD. This review may help in the design of future UPS‐related therapies for AD.
The blood-brain barrier (BBB) is a physiological regulator of transport of essential items from blood to brain for the maintenance of homeostasis of the central nervous system (CNS) within narrow ...limits. The BBB is also responsible for export of harmful or metabolic products from brain to blood to keep the CNS fluid microenvironment healthy. However, noxious insults to the brain caused by trauma, ischemia or environmental/chemical toxins alter the BBB function to small as well as large molecules e.g., proteins. When proteins enter the CNS fluid microenvironment, development of brain edema occurs due to altered osmotic balance between blood and brain. On the other hand, almost all neurodegenerative diseases and traumatic insults to the CNS and subsequent BBB dysfunction lead to edema formation and cell injury. To treat these brain disorders suitable drug therapy reaching their brain targets is needed. However, due to edema formation or only a focal disruption of the BBB e.g., around brain tumors, many drugs are unable to reach their CNS targets in sufficient quantity. This results in poor therapeutic outcome. Thus, new technology such as nanodelivery is needed for drugs to reach their CNS targets and be effective. In this review, use of nanowires as a possible novel tool to enhance drug delivery into the CNS in various disease models is discussed based on our investigations. These data show that nanowired delivery of drugs may have superior neuroprotective ability to treat several CNS diseases effectively indicating their role in future therapeutic strategies.
Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS), affecting mostly young-aged people. As a chronic incurable disease, in most cases, it can lead to progressive ...neurological impairment and severe disability. Depression and anxiety are major distress factors for MS patients, being considerably aggravating elements for their functional capacity. In this study, we analysed the mood disorder distribution and the possible correlations between depression, anxiety, automatic negative thoughts, and MS disability. We took into consideration 146 MS patients, who completed a series of questionnaires: Beck Depression Inventory II (BDI-II), Endler Multidimensional Anxiety Scales-State (EMAS-S), and Automatic Thoughts Questionnaire (ATQ). The Expanded Disability Status Scale (EDSS) was used to measure the neurological disability. Of all patients, 30.1% had symptoms for depression and 11% presented suicidal thoughts. After analysing the correlation index between each variable, we found that there is a mild positive correlation between depression and the EDSS score and between anxiety and the EDSS score. A difference is found in the test scores according to the type of the MS disease. Also, automatic negative thoughts are strongly correlated with depression and anxiety, but do not mediate the path between psychological comorbidities and neurological impairment. Sociodemographic features and interferon-beta treatment were not related to the intensity of the mood disorders. The study suggests that depression and anxiety are frequently encountered among MS patients and these mental disfunctions have an impact on their disability. A proper identification of these risk factors may improve the quality of life for these patients.
Recent advances in understanding the pathogenesis of multiple sclerosis (MS) have brought into the spotlight the major role played by reactive astrocytes in this condition. Response Gene to ...Complement (RGC)-32 is a gene induced by complement activation, growth factors, and cytokines, notably transforming growth factor β, that is involved in the modulation of processes such as angiogenesis, fibrosis, cell migration, and cell differentiation. Studies have uncovered the crucial role that RGC-32 plays in promoting the differentiation of Th17 cells, a subtype of CD4
+
T lymphocytes with an important role in MS and its murine model, experimental autoimmune encephalomyelitis. The latest data have also shown that RGC-32 is involved in regulating major transcriptomic changes in astrocytes and in favoring the synthesis and secretion of extracellular matrix components, growth factors, axonal growth molecules, and pro-astrogliogenic molecules. These results suggest that RGC-32 plays a major role in driving reactive astrocytosis and the generation of astrocytes from radial glia precursors. In this review, we summarize recent advances in understanding how RGC-32 regulates the behavior of Th17 cells and astrocytes in neuroinflammation, providing insight into its role as a potential new biomarker and therapeutic target.
•Task-specific dystonia (TSD) is triggered by skilled, repetitive actions.•Idiopathic adult-onset TSD of the lower limbs has seldom been reported.•Dystonia confined to the lower limbs leads to ...significant diagnosis delay.•Botulinum toxin injection can improve symptoms.
The aim of this trial was to investigate whether stroke patients who receive Cerebrolysin show improved motor function in the upper extremities at day 90 compared with patients who receive a placebo.
...This study was a prospective, randomized, double-blind, placebo-controlled, multicenter, parallel-group study. Patients were treated with Cerebrolysin (30 mL/d) or a placebo (saline) once daily for 21 days, beginning at 24 to 72 hours after stroke onset. The patients also participated in a standardized rehabilitation program for 21 days that was initiated within 72 hours after stroke onset. The primary end point was the Action Research Arm Test score on day 90.
The nonparametric effect size on the Action Research Arm Test score on day 90 indicated a large superiority of Cerebrolysin compared with the placebo (Mann-Whitney estimator, 0.71; 95% confidence interval, 0.63-0.79; P<0.0001). The multivariate effect size on global status, as assessed using 12 different outcome scales, indicated a small-to-medium superiority of Cerebrolysin (Mann-Whitney estimator, 0.62; 95% confidence interval, 0.58-0.65; P<0.0001). The rate of premature discontinuation was <5% (3.8%). Cerebrolysin was safe and well tolerated.
Cerebrolysin had a beneficial effect on function and global outcome in early rehabilitation patients after stroke. Its safety was comparable with that of the placebo, suggesting a favorable benefit/risk ratio. Because this study was exploratory and had a relatively small sample size, the results should be confirmed in a large-scale, randomized clinical trial.
URL: http://www.clinicaltrialsregister.eu. Unique identifier: 2007-000870-21.
Malnutrition is common after stroke and can affect rehabilitation and healthcare costs. A comprehensive overview of stroke patients' nutritional condition from the hyperacute to the chronic phase is ...lacking. This systematic review aimed to investigate the prevalence of impaired nutritional condition (INC) across the continuum of care in specific phases after stroke.
CAB ABSTRACTS, Embase, MEDLINE, were used to collect studies published between 01-01-1999 and 26-08-2020. Primary and secondary outcomes were prevalence of INC and prevalence of malnutrition, respectively. Exploratory outcomes were prevalence of INC at follow-up, nutritional examination methods, prevalence of dysphagia, stroke severity, adverse events, and continent-specific prevalence of INC. A random-effects meta-analysis model was used to estimate the phase-specific pooled prevalence of INC and malnutrition.
The dataset consisted of 78 study groups selected over a total of 1,244 identified records. The pooled prevalence of INC and malnutrition were 19% (95%CI:7-31) (
= 4) and 19% (95%CI:9-29) (
= 3), 34% (95%CI:25-43) (
= 34) and 26% (95%CI:18-35) (
= 29), 52% (95%CI:43-61) (
= 34) and 37% (95%CI:28-45) (
= 31), 21% (95%CI:12-31) (
= 3) and 11% (95%CI:0-24) (
= 3) and 72% (95%CI:41-100) (
= 3) and 30% (95%CI:0-76) (
= 2) in the hyperacute, acute, early subacute, late subacute, and chronic phase, respectively.
INC and malnutrition are highly prevalent in all stages of stroke care. Since malnutrition has been shown to negatively affect clinical outcomes, mortality, and overall healthcare expenditure in stroke survivors, it is essential to examine and monitor the nutritional status of stroke patients throughout their care journey to guide and plan, timely nutritional support and dietary modification.
From an interdisciplinary approach, the neurosciences (NSs) represent the junction of many fields (biology, chemistry, medicine, computer science, and psychology) and aim to explore the structural ...and functional aspects of the nervous system. Among modern neurophysiological methods that “measure” different processes of the human brain to salience stimuli, a special place belongs to eye tracking (ET). By detecting eye position, gaze direction, sequence of eye movement and visual adaptation during cognitive activities, ET is an effective tool for experimental psychology and neurological research. It provides a quantitative and qualitative analysis of the gaze, which is very useful in understanding choice behavior and perceptual decision making. In the high tech era, ET has several applications related to the interaction between humans and computers. Herein, ET is used to evaluate the spatial orienting of attention, the performance in visual tasks, the reactions to information on websites, the customer response to advertising, and the emotional and cognitive impact of various spurs to the brain.
Neuroregeneration is a relatively recent concept that includes neurogenesis, neuroplasticity, and neurorestoration--implantation of viable cells as a therapeutical approach.
Neurogenesis and ...neuroplasticity are impaired in brains of patients suffering from Alzheimer's Disease or Parkinson's Disease and correlate with low endogenous protection, as a result of a diminished growth factors expression. However, we hypothesize that the brain possesses, at least in early and medium stages of disease, a "neuroregenerative reserve", that could be exploited by growth factors or stem cells-neurorestoration therapies.
In this paper we review the current data regarding all three aspects of neuroregeneration in Alzheimer's Disease and Parkinson's Disease.
Gut microbiota, the total microorganisms in our gastrointestinal tract, might have an implication in multiple sclerosis (MS), a demyelinating neurological disease. Our study included 50 MS patients ...and 21 healthy controls (HC). Twenty patients received a disease modifying therapy (DMT), interferon beta1a or teriflunomide, 19 DMT combined with homeopathy and 11 patients accepted only homeopathy. We collected in total 142 gut samples, two for each individual: at the study enrolment and eight weeks after treatment. We compared MS patients' microbiome with HC, we analysed its evolution in time and the effect of interferon beta1a, teriflunomide and homeopathy. There was no difference in alpha diversity, only two beta diversity results related to homeopathy. Compared to HC, untreated MS patients had a decrease of Actinobacteria, Bifidobacterium, Faecalibacterium prauznitzii and increased Prevotella stercorea, while treated patients presented lowered Ruminococcus and Clostridium. Compared to the initial sample, treated MS patients had a decrease of Lachnospiraceae and Ruminococcus and an increased Enterococcus faecalis. Eubacterium oxidoreducens was reduced after homeopathic treatment. The study revealed that MS patients may present dysbiosis. Treatment with interferon beta1a, teriflunomide or homeopathy implied several taxonomic changes. DMTs and homeopathy might influence the gut microbiota.
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•Multiple sclerosis patients have a distinct gut microbiota compared to healthy controls.•Treatment with interferon beta1a, teriflunomide or homeopathy implies various changes of gut microbiota.•Medication mildly influences beta diversity, with no significant effect on the overall alpha diversity.
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