Kind Of Neurodegenerative Disease Research Articles

DNA methylation: The epigenetic mechanism of Alzheimer's disease.

Nowadays, with the development of the social health care system, there is an increasing trend towards an aging society. The incidence of Alzheimer's disease (AD) is also on the rise. AD is a kind of neurodegenerative disease that can be found in any age group. For years, scientists have been committing to discovering the cause of AD. DNA methylation is one of the most common epigenetic mechanisms in mammals and plays a vital role in the pathogenesis of several diseases, including tumors. Studying chemical changes in the epigenome, or DNA methylation can help us understand the effects of our environment and life on diseases, such as smoking, depression, and menopause, which may affect people's chances of developing Alzheimer's or other diseases. Recent studies have identified some crucial genes like ANK1, RHBDF2, ABCA7, and BIN1, linking DNA methylation to AD. This review focuses on elucidating the relationship between DNA methylation and the pathogenesis of AD and provides an outlook on possible targeted therapeutic modalities.

Role of microglia autophagy and mitophagy in age-related neurodegenerative diseases.

Microglia, characterized by responding to damage, regulating the secretion of soluble inflammatory mediators, and engulfing specific segments in the central nervous system (CNS), function as key immune cells in the CNS. Emerging evidence suggests that microglia coordinate the inflammatory responses in CNS system and play a pivotal role in the pathogenesis of age-related neurodegenerative diseases (NDDs). Remarkably, microglia autophagy participates in the regulation of subcellular substances, which includes the degradation of misfolded proteins and other harmful constituents produced by neurons. Therefore, microglia autophagy regulates neuronal homeostasis maintenance and process of neuroinflammation. In this review, we aimed at highlighting the pivotal role of microglia autophagy in the pathogenesis of age-related NDDs. Besides the mechanistic process and the co-interaction between microglia autophagy and different kinds of NDDs, we also emphasized potential therapeutic agents and approaches that could be utilized at the onset and progression of these diseases through modulating microglia autophagy, including promising nanomedicines. Our review provides a valuable reference for subsequent studies focusing on treatments of neurodegenerative disorders. The exploration of microglia autophagy and the development of nanomedicines greatly enhances current understanding of NDDs.

Virome analysis provides new insights into the association between viruses and Parkinson's disease.

Parkinson's disease (PD) is a kind of neurodegenerative disease that causes a huge burden to society. Previous studies have suggested the association between PD and multiple viruses. However, there is still a lack of a virome study about PD. This study systematically identified viruses from the public RNA-sequencing data of more than 700 samples from both PD patients and the control group (most were healthy people). Only nine viruses such as human betaherpesvirus 5 and Merkel cell polyomavirus have been detected in several human brain tissues of the central nervous system, the appendix, and blood of PD patients, and all of these viruses were also detected in the control group. Most viruses were observed to have low abundance in no more than three tissues. No statistically significant differences were observed between the virus abundance in the PD patients and the control group for all viruses. The positive rates of most viruses in PD patients were higher or similar to that in the control group, although those were less than 5% for most viruses. Overall, this is the first study to systematically investigate the virome in PD patients, and provides new insights into the association between viruses and PD.

The Role of TDP-43 in Neurodegenerative Disease.

In recent years, more and more neurodegenerative diseases, such as ALS, FTLD and AD, have been found to share a common pathological feature, which is the depletion of TDP-43 in the nucleus and the accumulation of TDP-43 in the cytoplasm through hyperphosphorylation, ubiquitination and cleavage. Therefore, this kind of neurodegenerative disease is also called TDP-43 proteinopathy. This suggests that TDP-43 plays a role in the pathogenesis of disease. Current studies show that the pathophysiological mechanism of TDP-43 in neurodegeneration is very complex. In this review, we describe the structure of TDP-43, its main physiological functions, the possible pathogenesis and how TDP-43 provides a new pathway to treat neurodegenerative diseases.

Progress in the Mechanism of Autophagy and Traditional Chinese Medicine Herb Involved in Dementia.

Dementias is a kind of neurodegenerative disease, which occurs among the aging population. Current therapeutic outcome for dementia is limited. The medical use of herbal plant has a rich history in traditional Chinese medicine practice for thousands of years. Herbal medicine (HM) may provide a positive effect for prevention and treatment in dementia. As an alternative treatment to dementia, there has been a growing interest in HM extracts in scientific community as a result of its promising study results, mainly in animal experiment. At the molecular level, HM extracts trigger autophagy and reduce generation of reactive oxygen species (ROS) while inhibiting inflammation and reduce neurotoxicity. Experiments both in vivo and in vitro have identified certain potential of HM extracts and natural products as an important regulator factor in mediating autophagy, which might contribute to the improvement of dementia. This brief review not only summarizes the mechanism of autophagy in dementia but also offers a general understanding of the therapeutic mechanism of HM extracts in treating dementia and evaluates the potential clinical practice of HM in general.

Identification of the function and mechanism of m6A reader IGF2BP2 in Alzheimer's disease.

Alzheimer’s disease, the most common form of dementia in the elderly, is a kind of neurodegenerative disease. However, its pathogenesis and diagnosis remain unclear. M6A is related to nervous system development and neurodegenerative diseases. Here in this study, using multiple RNA-seq datasets of Alzheimer’s brain tissues, along with bioinformatic analysis, we innovatively found that m6A reader protein IGF2BP2 was abnormally highly expressed in Alzheimer’s patients. After compared between Alzheimer’s and normal brain samples, and between IGF2BP2- high and IGF2BP2- low subgroups of Alzheimer’s patients, we took the shared differentially expressed genes as the relevant gene sets of IGF2PB2 affecting Alzheimer’s disease occurrence for subsequent analysis. Then, weight gene correlation analysis was conducted and 17 functional modules were identified. The module that most positively correlated with Alzheimer’s disease and IGF2PB2-high subgroups were mainly participated in ECM receptor interaction, focal adhesion, cytokine-cytokine receptor interaction, and TGF-beta signaling pathway. Afterwards, a hub gene-based model including 20 genes was constructed by LASSO regression and validated by ROC curve for Alzheimer diagnosis. Finally, we preliminarily elucidated that IGF2BP2 could bind with mRNAs in a m6A-dependent manner. This study first elucidates the pathogenic role of IGF2BP2 in Alzheimer’s disease. IGF2BP2 and its relevant m6A modifications are potential to be new diagnostic and therapeutic targets for Alzheimer’s patients.

Metabolic disorder in Alzheimer's disease.

Alzheimer's disease (AD), a well known aging-induced neurodegenerative disease is related to amyloid proteinopathy. This proteinopathy occurs due to abnormalities in protein folding, structure and thereby its function in cells. The root cause of such kind of proteinopathy and its related neurodegeneration is a disorder in metabolism, rather metabolomics of the major as well as minor nutrients. Metabolomics is the most relevant "omics" platform that offers agreat potential for the diagnosis and prognosis of neurodegenerative diseases as an individual's metabolome. In recent years, the research on such kinds of neurodegenerative diseases, especially aging-related disorders is broadened its scope towards metabolic function. Different neurotransmitter metabolisms are also involved with AD and its associated neurodegeneration. The genetic and epigenetic backgrounds are also noteworthy. In this review, the physiological changes of AD in relation to its corresponding biochemical, genetic and epigenetic involvements including its (AD) therapeutic aspects are discussed.

Neuroprotection: Targeting Multiple Pathways by Naturally Occurring Phytochemicals.

With the increase in the expectancy of the life span of humans, neurodegenerative diseases (NDs) have imposed a considerable burden on the family, society, and nation. In defiance of the breakthroughs in the knowledge of the pathogenesis and underlying mechanisms of various NDs, very little success has been achieved in developing effective therapies. This review draws a bead on the availability of the nutraceuticals to date for various NDs (Alzheimer’s disease, Parkinson’s disease, Amyotrophic lateral sclerosis, Huntington’s disease, vascular cognitive impairment, Prion disease, Spinocerebellar ataxia, Spinal muscular atrophy, Frontotemporal dementia, and Pick’s disease) focusing on their various mechanisms of action in various in vivo and in vitro models of NDs. This review is distinctive in its compilation to critically review preclinical and clinical studies of the maximum phytochemicals in amelioration and prevention of almost all kinds of neurodegenerative diseases and address their possible mechanism of action. PubMed, Embase, and Cochrane Library searches were used for preclinical studies, while ClinicalTrials.gov and PubMed were searched for clinical updates. The results from preclinical studies demonstrate the efficacious effects of the phytochemicals in various NDs while clinical reports showing mixed results with promise for phytochemical use as an adjunct to the conventional treatment in various NDs. These studies together suggest that phytochemicals can significantly act upon different mechanisms of disease such as oxidative stress, inflammation, apoptotic pathways, and gene regulation. However, further clinical studies are needed that should include the appropriate biomarkers of NDs and the effect of phytochemicals on them as well as targeting the appropriate population.

Phoenixin-20 Ameliorates Lipopolysaccharide-Induced Activation of Microglial NLRP3 Inflammasome.

Injury associated with neuroinflammation has been linked with several kinds of neurodegenerative diseases. The activation of the NLRP3 inflammasome plays an important role in microglia-mediated inflammation. Phoenixin (PNX)-20 is a newly discovered neuropeptide with pleiotropic effects involved in the regulation of reproductive and cognitive function, depression, and food uptake. This study investigated whether PNX-20 possesses a protective effect against lipopolysaccharide (LPS)-induced activation of the NLRP3 inflammasome in microglia. Firstly, our results show that the PNX-20 treatment significantly prevented LPS-induced expression of NADPH oxidase 4 (NOX-4) and the generation of reactive oxygen species (ROS). Secondly, PNX-20 mitigated LPS-induced upregulation of TxNIP, an upstream regulator of NLRP3 inflammasome activation. Thirdly, further evaluation of the major components of the NLRP3 inflammasome revealed that PNX-20 inhibited LPS-mediated upregulation of NLRP3, ASC, and cleaved caspase-1 (P10). Notably, based on our results, the inhibitory effect of PNX-20 on the NLRP3 inflammasome results in the inhibition of IL-1β and IL-18 secretions. Finally, we found that PNX-20 ameliorated the reduction in SIRT1 expression induced by LPS. When microglial SIRT1 was inhibited by nicotine, PNX-20 lost its suppressive effect on the expression of NLRP3, ASC, and caspase-1, as well as the secretion of IL-1β and IL-18. As a result of these findings, we draw the conclusion that the neuroprotective effect of PNX-20 is dependent on SIRT1. Collectively, the study shows that PNX-20 has a regulatory effect via modulation of neuroinflammation.

Clinical, MRI and 18F-FDG-PET/CT analysis of progressive supranuclear palsy

BackgroundProgressive supranuclear palsy (PSP) is a kind of neurodegenerative disease. In the present study, the clinical and magnetic resonance imaging (MRI) features of PSP were analyzed, and fluorodeoxyglucose positron emission tomography (FDG PET) brain imaging was performed to preliminarily explore the characteristics of cerebral glucose metabolism, so as to make a more accurate and differential diagnosis. MethodsIn accordance with the diagnostic criteria, the clinical symptoms, the unified Parkinson’s disease rating scale (UPDRS), the mini-mental state examination (MMSE), the activities of daily living (ADL), and the magnetic resonance image (MRI) of 19 patients with PSP were examined and FDG-PET brain imaging was performed. Visual analysis and statistical parameter diagram were used to analyze the characteristics. ResultsConcerning the clinical characteristics, 84.21% of the patients with PSP had early recurrent falls, 63.15% had vertical supranuclear ophthalmoplegia, and 47.37% had symptoms of dementia. The MRI scans showed that 57.89% of the patients had a “hummingbird” sign in the middle sagittal position. The FDG-PET imaging indicated that glucose metabolism in the midbrain and frontal lobe was decreased in patients with PSP. ConclusionsStudying the clinical and MRI features of patients with PSP can be helpful in the diagnosis, especially as some signs could be found in the early stage by FDG PET, enhancing early diagnosis and differentiation.

Circulating MicroRNAs as Diagnostic Biomarkers for Motor Neuron Disease.

Motor neuron disease (MND) is a kind of neurodegenerative disease that selectively invades spinal cord anterior horn cells, brainstem motor neurons, cortical pyramidal cells and the pyramidal tract. The main clinical features are the symptoms and signs of impaired upper and lower motor neurons, manifested as muscle weakness, atrophy and pyramidal tract signs. Histopathology has shown the disappearance of pyramidal cells in the motor cortex, loss of motor neurons in the anterior horn of the spinal cord and brainstem, and degeneration of the corticospinal tract. Due to the lack of effective treatment methods, the prognosis is generally poor, so it is of great significance to confirm the diagnosis early by various means. However, the current diagnosis of MND mainly relies on the combination of clinical manifestations and neurophysiological examinations, lacking effective means of early diagnosis. Circulating microRNA (CmiRNA) is a kind of stable miRNA molecule in serum, plasma and other body fluids, which has the characteristics of distinct differential expression, sensitive detection and convenient sample collection. As a possible new biomarker of MND, CmiRNA can not only reveal the pathophysiological process of MND, but also monitor disease progression and response to drug therapy. With the development of miRNA detection technology, more and more CmiRNAs as biomarkers with potential diagnostic value have been investigated. In this review, we explored the possibility of circulating samples as different sources of biomarkers for the diagnosis of MND, analyzing the progress of CmiRNA detection techniques, and presenting potential diagnostic MND biomarkers that have been reported.

Predicting Sub-Golgi Apparatus Resident Protein With Primary Sequence Hybrid Features

The Golgi apparatus is a significant membrane-bound organelle of eukaryotic cells that is made up of a series of flattened, stacked pouches (called cisternae). The Golgi apparatus packages proteins into membrane-bound vesicles, and so it is responsible for transporting, modifying, and packaging proteins and lipids into vesicles for delivery to targeted destinations. It belongs to the central organelle mediating system of eukaryotic cells. Functional defects of the Golgi apparatus are associated with many kinds of neurodegenerative diseases, such as Parkinson's and Alzheimer's diseases. Golgi-resident proteins play an important role in the Golgi apparatus' processing, which includes storing, packaging, and dispatching proteins. Identifying sub-Golgi protein types can help researchers to develop more effective therapies and drugs for diseases that result from disorders of Golgi-resident proteins. In this paper, we propose a computational model to discriminate cis-Golgi proteins from trans-Golgi proteins using a machine learning method. First, we use PseKNC, K-separated Bigrams, and PsePSSM as feature extraction techniques, and then we select the optimal features among those identified by PseKNC with the AdaBoost classifier. To create a balanced dataset out of the imbalanced set of Golgi proteins, we used the Random-SMOTE oversampling approach. Finally, we employed the SVM algorithm to distinguish cis-Golgi proteins from trans-Golgi proteins. The proposed method achieves promising performance, with accuracy of 96.5%, 96.5%, and 96.9% in the experiments with jackknife cross-validation, independent testing, and 10-fold cross-validation, respectively, which exceeds the performance of previous related work.

Meditation enhances brain oxygenation, upregulates BDNF and improves quality of life in patients with primary open angle glaucoma: A randomized controlled trial.

Glaucoma (POAG) is a kind of neurodegenerative disease known to be closely associated with stress and adverse quality of life (QOL). Stress has also been shown to be involved in etiopathogenesis of primary open angle glaucoma (POAG). Complementary treatment in form of Meditation has been reported to improve QOL, brain oxygenation and decrease markers of stress. With this premise, a randomized controlled trial was carried out to assess the effect of Meditation on intraocular pressure, subjective QOL and objective markers of stress and brain oxygenation in patients with POAG. Sixty patients were randomized into intervention and control groups. Intervention group underwent 45 minutes of Meditation daily for 6 weeks in addition to standard medical treatment while controls received only standard medical treatment. Inclusion criteria were patients with POAG, age >45 years, best corrected visual acuity >6/60. Patients with other ocular co-morbid conditions contributing to vision loss, systemic diseases, patients already practicing meditation in any form were excluded. An assessment of IOP, brain oxygenation using functional near infrared spectroscopy (fNIRS), QOL (WHO-BREF QOL) and stress markers in serum (cortisol, β-endorphins, interleukin-6, brain derived neurotrophic factor (BDNF), reactive oxygen species) was made at baseline and at 6 weeks. 21 female and 39 male patients were enrolled with a mean age of 57.28±9.37 years. All parameters were comparable between two groups at baseline. At 6 weeks mean level of IOP decreased significantly in intervention group (15.9±1.8 mmHg to 14.4±1.21 mm Hg, p-value 0.0001) as compared to control group (15.7±1.4 mmHg to 15.65±1.41, p-value 0.41). fNIRS showed significant improvement in oxygenated hemoglobin change (ΔHbO) in intervention group in the prefrontal cortex (p-value < 0.0001) as compared to control group (p-value 0.52). WHO-BREF QOL score increased significantly in intervention group (86.6±6.16 to 93.3±5.66, p-value 0.0001) as compared to control (89±7.25 to 89.07±3.24, p-value 0.74).Mean serum cortisol decreased significantly in intervention group (497±46.37 ng/ml to 447±53.78 ng/ml, p-value 0.01) as compared to control group (519.75±24.5 to 522.58±26.63 ng/ml, p-value 0.64). Mean β-endorphin levels increased significantly (33±5.52pg/ml to 43.27pg/ml, p-value < 0.0001) as compared to control group (34.78±4.1pg/ml to 36.33pg±4.07pg/ml p-value 0.27). Interleukin-6 decreased significantly in intervention group (2.2±0.5 ng/ml to 1.35±0.32 ng/ml, p-value < 0.0001) as compared to control group (2.03±0.37 to 2.17±0.34 ng/ml p-value 0.25). BDNF increased significantly in intervention group (52.24±6.71 to 63.25±13.48 ng/ml p-value 0.004) as compared to control group (53.23±5.82 to 54.42±5.66 ng/ml p-value 0.54). ROS decreased significantly in intervention group (1596.19±179.14 to 1261±244.31 RLU/min/104 neutrophils p-value 0.0001) as compared to control group (1577.5±172.02 to 1662.5±84.75 RLU/min/104 neutrophils p-value 0.16). A short term course of Meditation was associated with significant improvement in brain oxygenation and QOL along with a reduction in IOP and stress markers. Meditation may be a useful as an adjunct to standard treatment in patients with POAG and potentially decrease the risk of glaucoma progression.

Neuroimmunological Implications of AQP4 in Astrocytes.

The brain has high-order functions and is composed of several kinds of cells, such as neurons and glial cells. It is becoming clear that many kinds of neurodegenerative diseases are more-or-less influenced by astrocytes, which are a type of glial cell. Aquaporin-4 (AQP4), a membrane-bound protein that regulates water permeability is a member of the aquaporin family of water channel proteins that is expressed in the endfeet of astrocytes in the central nervous system (CNS). Recently, AQP4 has been shown to function, not only as a water channel protein, but also as an adhesion molecule that is involved in cell migration and neuroexcitation, synaptic plasticity, and learning/memory through mechanisms involved in long-term potentiation or long-term depression. The most extensively examined role of AQP4 is its ability to act as a neuroimmunological inducer. Previously, we showed that AQP4 plays an important role in neuroimmunological functions in injured mouse brain in concert with the proinflammatory inducer osteopontin (OPN). The aim of this review is to summarize the functional implication of AQP4, focusing especially on its neuroimmunological roles. This review is a good opportunity to compile recent knowledge and could contribute to the therapeutic treatment of autoimmune diseases through strategies targeting AQP4. Finally, the author would like to hypothesize on AQP4’s role in interaction between reactive astrocytes and reactive microglial cells, which might occur in neurodegenerative diseases. Furthermore, a therapeutic strategy for AQP4-related neurodegenerative diseases is proposed.

Oxytocin inhibits lipopolysaccharide-induced inflammation in microglial cells and attenuates microglial activation in lipopolysaccharide-treated mice.

BackgroundOveractivated microglia is involved in various kinds of neurodegenerative diseases. Suppression of microglial overactivation has emerged as a novel strategy for treatment of neuroinflammation-based neurodegeneration. In the current study, anti-inflammatory effects of oxytocin (OT), which is a highly conserved nonapeptide with hormone and neurotransmitter properties, were investigated in vitro and in vivo.MethodsBV-2 cells and primary microglia were pre-treated with OT (0.1, 1, and 10 μM) for 2 h followed by LPS treatment (500 ng/ml); microglial activation and pro-inflammatory mediators were measured by Western blot, RT-PCR, and immunofluorescence. The MAPK and NF-κB pathway proteins were assessed by Western blot. The intracellular calcium concentration ([Ca2+]i) was determined using Fluo2-/AM assay. Intranasal application of OT was pre-treated in BALB/C mice (adult male) followed by injected intraperitoneally with LPS (5 mg/kg). The effect of OT on LPS-induced microglial activation and pro-inflammatory mediators was measured by Western blot, RT-PCR, and immunofluorescence in vivo.ResultsUsing the BV-2 microglial cell line and primary microglia, we found that OT pre-treatment significantly inhibited LPS-induced microglial activation and reduced subsequent release of pro-inflammatory factors. In addition, OT inhibited phosphorylation of ERK and p38 but not JNK MAPK in LPS-induced microglia. OT remarkably reduced the elevation of [Ca2+]i in LPS-stimulated BV-2 cells. Furthermore, a systemic LPS-treated acute inflammation murine brain model was used to study the suppressive effects of OT against neuroinflammation in vivo. We found that pre-treatment with OT showed marked attenuation of microglial activation and pro-inflammatory factor levels.ConclusionsTaken together, the present study demonstrated that OT possesses anti-neuroinflammatory activity and might serve as a potential therapeutic agent for treating neuroinflammatory diseases.

A case of nocturnal frontal lobe epilepsy in a patient with spinocerebellar ataxia type 17

Nocturnal frontal lobe epilepsy (NFLE) comprises a complex spectrum of distinct paroxysmal sleep-related attacks of variable intensity, including paroxysmal arousals, nocturnal paroxysmal dystonias and epileptic nocturnal wanderings. Scalp EEG and brain MRI are unable to reveal abnormalities in a considerable amount of patients. In those cases the epileptic nature of NFLE is supported by the stereotypical clinical presentation of the episodes and the often dramatic response to antiepileptic drugs (AEDs) like Carbamazepine, Clonazepam or Topiramate. Spinocerebellar ataxia type 17 (SCA 17) is a neurodegenerative disease caused by the expansion above 44 units of a CAG/CAA repeat in the coding region of the TATA box binding protein (TBP) gene. It is one of the rarer forms amongst autosomal dominant cerebellar ataxias, with extreme variable age at onset and clinical phenotype. Epilepsy is quite commonly observed among SCA 17 patients, however it is exclusively described in terms of generalized tonic–clonic seizures. We report a case of NFLE occurring in a SCA 17 patient and brilliantly responsive to Topiramate after failure of the first line therapy with Carbamazepine.

Invasive and Non-invasive Methods in Diagnostic of Migraine: a Literature Review

Invasive and Non-invasive Methods in Diagnostic of Migraine: a Literature ReviewMigraine is one of the most common neurological disorders worldwide. Prevalence varies in different reports but on average it is up to 15% of adults, mostly women, and up to 14,5 % in school age children. Although the diagnosis of migraine in children is not easy, migraine prevalence of migraine in childhood is very high. Morbidity of migraine is strongly related to positive family history and it illustrates ascertain close relation to genetic matter. Medical and social burden of migraine is tremendous since it affects all range of ages, starting from young children to seniors, and severe attacks can be even as disabling as quadriplegia. Despite there are thousands of trials done, indisputable cause of migraine as well as pathophysiological treatment is not clear. There are several forms of migraine, two of which are the most common- migraine without aura and migraine with aura. Diagnosis of migraine is based mainly on anamnesis data and clinical symptoms according to The International Classification of Headache Disorders (ICHD), neuroimaging is recommended only in case of so called red flag symptoms and is oriented to exclude secondary headache. Invasive investigations such as lumbar puncture and angiography with contrast are integral parts of investigational plan when migraine has to be differentiated from subarachnoid haemorrhage or pulmonary and cardiac right-to-left shunts. Modern neuroimaging reveals migraine as a kind of neurodegenerative disease that in severe and/or frequent form leads to brain white matter lesions, subclinical infarcts in the posterior circulation and increased iron deposition in brain. On the scientific laboratory level, it is possible now to diagnose migraine on affirmative base, and this is believed to be the future of neuroimaging in clinical practice regarding migraine.

Risperidone significantly inhibits interferon-γ-induced microglial activation in vitro

Microglia has recently been regarded to be a mediator of neuroinflammation via the release of proinflammatory cytokines, nitric oxide (NO) and reactive oxygen species (ROS) in the central nervous system (CNS). Microglia has thus been reported to play an important role in the pathology of neurodegenerative disease, such as Alzheimer's disease (AD) and Parkinson's disease (PD). The pathological mechanisms of schizophrenia remain unclear while some recent neuroimaging studies suggest even schizophrenia may be a kind of neurodegenerative disease. Risperidone has been reported to decrease the reduction of MRI volume during the clinical course of schizophrenia. Many recent studies have demonstrated that immunological mechanisms via such as interferon (IFN)-γ and cytokines might be relevant to the pathophysiology of schizophrenia. In the present study, we thus investigated the effects of risperidone on the generation of nitric oxide, inducible NO synthase (iNOS) expression and inflammatory cytokines: interleukin (IL)-1β, IL-6 and tumor necrosis factor (TNF)-α by IFN-γ-activated microglia by using Griess assay, Western blotting and ELISA, respectively. In comparison with haloperidol, risperidone significantly inhibited the production of NO and proinflammatory cytokines by activated microglia. The iNOS levels of risperidone-treated cells were much lower than those of the haloperidol-treated cells. Antipsychotics, especially risperidone may have an anti-inflammatory effect via the inhibition of microglial activation, which is not only directly toxic to neurons but also has an inhibitory effect on neurogenesis and oligodendrogenesis, both of which have been reported to play a crucial role in the pathology of schizophrenia.

National survey of contraceptive services in STD clinics

Neurodegenerative diseases (NDs) represent a common neurological pathology that determines a progressive deterioration of the brain or the nervous system. For treating NDs, comprehensive and alternative medicines have attracted scientific researchers' attention recently. Edible mushrooms are essential for preventing several age-based neuronal dysfunctions such as Parkinson's and Alzheimer's diseases. Mushroom such as Grifola frondosa, Lignosus rhinocerotis, Hericium erinaceus, may improve cognitive functions. It has also been reported that edible mushrooms (basidiocarps/mycelia extracts or isolated bioactive compounds) may reduce beta-amyloid-induced neurotoxicity. Medicinal mushrooms are being used for novel and natural compounds that help modulate immune responses and possess anti-cancer, anti-microbial, and anti-oxidant properties. Compounds such as polyphenols, terpenoids, alkaloids, sesquiterpenes, polysaccharides, and metal chelating agents are validated in different ND treatments. This review aims to assess mushrooms' role and their biomolecules utilization for treating different kinds of NDs. The action mechanisms, presented here, including reducing oxidative stress, neuroinflammation, and modulation of acetylcholinesterase activity, protecting neurons or stimulation, and regulating neurotrophins synthesis. We also provide background about neurodegenerative diseases and in-silico techniques of the drug research. High costs associated with experiments and current ethical law imply efficient alternatives with limited cost value. In silico approaches provide an alternative method with low cost that has been successfully implemented to cure ND disorders in recent days. We also describe the applications of computational procedures such as molecular docking, virtual high-throughput screening, molecular dynamic (MD) simulation, quantum-mechanical methods for drug design. They were reported against various targets in NDs.