Degenerative Disease Of Central Nervous System Research Articles

Lexical Retrieval Performance in Patients with Normal Pressure Hydrocephalus and Parkinson’s Disease

Objectives: This study aimed to investigate lexical retrieval performance in patients with similar patterns but different central nervous system degenerative diseases, specifically normal pressure hydrocephalus (NPH) and Parkinson’s disease (PD).Methods: A lexical retrieval task was performed on 14 patients with NPH, 14 patients with PD, and 14 healthy elderly subjects (HE) to compare their correct response scores, reaction times, and error types, and the Korean-Boston naming test (K-BNT) was additionally performed to determine the validity of the lexical retrieval task.Results: First, there was no significant difference in scores between the three groups on the K-BNT. Second, the scores of the NPH and PD groups were significantly lower than the HE group on the lexical retrieval task. Third, only the NPH group was significantly slower than the HE group in the reaction time on the lexical retrieval task. Fourth, the error type analysis showed that the NPH group made significantly more semantic and nonword errors and the PD group made significantly more semantic errors than the HE group. Fifth, the correlation analysis showed a significant static correlation between K-BNT and the lexical retrieval task scores with a correlation coefficient of .721.Conclusion: We suggest that the lexical retrieval task may be useful in the screening and differential diagnosis of patients with NPH and PD.

Age-related changes in meningeal lymphatic function are closely associated with vascular endothelial growth factor-C expression

Meningeal lymphatic vessels (MLVs) have crucial roles in removing metabolic waste and toxic proteins from the brain and transporting them to the periphery. Aged mice show impaired meningeal lymphatic function. Nevertheless, as the disease progresses, and significant pathological changes manifest in the brain, treating the condition becomes increasingly challenging. Therefore, investigating the alterations in the structure and function of MLVs in the early stages of aging is critical for preventing age-related central nervous system degenerative diseases. We detected the structure and function of MLVs in young, middle-aged, and aged mice. Middle-aged mice, compared with young and aged mice, showed enhanced meningeal lymphatic function along with MLV expansion and performed better in the Y maze test. Moreover, age-related changes in meningeal lymphatic function were closely associated with vascular endothelial growth factor-C (VEGF-C) expression in the brain cortex. Our data suggested that the cerebral cortex may serve as a target for VEGF-C supplementation to ameliorate meningeal lymphatic dysfunction, thus providing a new strategy for preventing age-related central nervous system diseases.

Pathophysiology of Cardiac Cell Injury in Post-COVID-19 Syndrome

Abstract: Recently, the scientific community has realized that COVID-19 effects are not limited to the acute period of infection but continue beyond that to cause more prolonged pathological changes. Post-COVID syndrome is a novel concept that describes the sequelae/persistent pathophysiological changes of post-COVID-19 infection. The current hypothesis suggests the involvement of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in cardiac arrhythmias, coronary artery aneurism, acute renal injury, central nervous system degenerative diseases, vascular endothelial cell dysfunction, and pulmonary dyspnea, as well as fibrotic lung damage. Therefore, COVID-19 has been identified as a poly-syndromic and poly-systemic inflammatory disease. Post-COVID extrapulmonary complications have been observed in approximately 85% of hospitalized COVID-19 survivors and 35% of COVID-19 outpatients. Furthermore, 25% of hospitalised COVID-19 survivors developed myocardiopathy.

Detection of Ferroptosis in Models of Brain Diseases.

Ferroptosis is a regulated form of non-apoptotic cell death driven by iron-dependent lipid peroxidation. In the past decade, ferroptosis has been reported to be involved in the pathological role in the central nervous system degenerative diseases (e.g., Alzheimer's disease, Huntington's disease, and Parkinson's disease), stroke, traumatic brain injury, and brain tumor. However, how to reliably detect and classify ferroptosis from other cell death in pathological conditions remains a great challenge, especially in primary brain cells and brain tissues. Here, we summarize the methods and protocols (such as real-time PCR, western blotting, immunofluorescence staining, lipid peroxidation assay kits and probe, immunofluorescence staining, GPX activity and glutathione depletion assay kits, iron detection, and TEM) used in the present study to detect and classify ferroptosis in the brain.

TUBB1, TUBA4A and MAPK as Indicators of Die-Back Degenerative Central Nervous System Disease in Patients Sickened by Specific Exposure to the Interior Environment of Water- Damaged Buildings

Beginning with Possible Estuarine Associated Syndrome (PEAS) in 1998 and followed by numerous studies on similar types of exposures, patients with illness associated with biotoxin exposure routinely have had symptom rosters dominated by executive cognitive dysfunction, including recent memory deficits, difficulty in concentration, difficulty with word finding, decreased assimilation of new knowledge, confusion and disorientation, tremors, headaches, vertigo, and unusual pains. In addition, tremors, headaches, vertigo, unusual pains and metallic taste. Toxins involved variously have included those found in toxin-forming dinoflagellates, including Pfiesteria and ciguatera; cyanobacteria, including Microcystis, Cylindrospermopsis and Lyngbya wollei; post Lyme syndrome and Babesia; as well as organisms found in damp buildings, including Aspergillus versicolor and A. penicillioides, Stachybotrys chartarum, Chaetomium globosum, Wallemia sebi, Actinobacteria species, especially Corynebacteria tuberculostearicum and Propionibacterium acnes; as well as bacterial endotoxins and beta-glucans. These illnesses have been called chronic inflammatory response syndromes (CIRS). The mechanism of neurologic findings has remained elusive despite studies showing successful treatment with intranasal vasoactive intestinal polypeptide (VIP). Neurocognitive testing has only been performed in PEAS patients, showing profound deficits in learning and higher cognitive functioning. These CIRS patients have had brain imaging without consistent findings, including MRI, EEG, and CT of the brain. NeuroQuant has shown findings that fit a “fingerprint” found in patients with specific causation and confirmed exposure to Actinobacteria and endotoxins. Fungal exposure shows disproportionate enlargement due to interstitial edema in the forebrain parenchyma and cortical grey, with a diminished caudate nucleus size. These findings have not been found in controls. The recent inclusion of transcriptomic studies using GENIE has confirmed that specific causation can be identified for Actinobacteria (48% of total confirmed cases), bacterial endotoxins (28%) and fungi (7%) in CIRS patients. The combination of NeuroQuant and GENIE has implicated excessive production of cytoskeletal tubulin genes TUBA4A and TUBB1 as risk factors for specific fingerprints for die-back degenerative central nervous system (CNS) injury in patients with illnesses associated variously with exposure to Actinobacteria, fungi and endotoxins. This study seeks to implicate a causal abnormality of excessive expression of tubulin genes TUBA4A and TUBB1. Given the role of these genes in die-back CNS degenerative diseases, such as Alzheimer’s, amyotrophic lateral sclerosis and Parkinson’s disease, and anecdotal successful treatment of CIRS patients with elevated TUBA4A and TUBB1, we suggest the possibility of treatment of tubulin excess may have a role in clinical improvement seen in die-back CNS degenerative diseases. Elevated levels of MAPK are also risk factors when combined with elevated levels of TUBA4A and TUBBI.

Amelioration of Experimental Autoimmune Encephalomyelitis in Alzheimer's Disease Mouse Models: A Potential Role for Aβ.

Emerging data have highlighted the coexistence of multiple sclerosis (MS) and Alzheimer’s disease (AD), both of which are common central nervous system degenerative diseases with a heavy burden on patients, their families, and society. However, it is unclear how MS progresses under an AD pathological background. We aimed to address the question of how MS progresses under an AD pathological background. We induced the experimental autoimmune encephalomyelitis (EAE) model of MS in two types of AD mouse models, Tg6799 and APP/PS1 mice. We found that, compared with wild-type mice, the clinical symptoms of EAE were significantly ameliorated in APP/PS1 mice but not in Tg6799 mice. Moreover, a much lower level of serum Aβ was observed in Tg6799 mice. EAE clinical symptoms in Tg6799 and C57BL/6J mice were ameliorated by intraperitoneal injection of Aβ42. Peripheral administration of Aβ42 peptides was able to inhibit Th17 development in vivo, which is likely to occur through the inhibition of IL-6 production in dendritic cells. Our findings revealed that AD and EAE could coexist in the same mouse, and Aβ residing in peripheral circulation likely plays an anti-inflammatory role in preventing EAE progression. These findings reveal the potential benefit of Aβ, one of the supervillains of AD, at least in certain contexts.

Fibroblast growth factors and their effect on cognitive functions and the course of central nervous system degenerative diseases

Fibroblast growth factors and their effect on cognitive functions and the course of central nervous system degenerative diseases

Programmed Cell Death Protein 1 Blockade Reduces Glycogen Synthase Kinase 3β Activity and Tau Hyperphosphorylation in Alzheimer's Disease Mouse Models.

Alzheimer’s disease (AD) is a central nervous system degenerative disease, with no effective treatment to date. Administration of immune checkpoint inhibitors significantly reduces neuronal damage and tau hyperphosphorylation in AD, but the specific mechanism is unclear. Here, we found that programmed cell death-receptor 1 (PD1) and its ligand PDL1 were induced by an intracerebroventricular injection of amyloid-β; they were significantly upregulated in the brains of APP/PS1, 5×FAD mice and in SH-SY5Y-APP cell line compared with control. The PD1 and PDL1 levels positively correlated with the glycogen synthase kinase 3 beta (GSK3β) activity in various AD mouse models, and the PDL1-GSK3β immune complex was found in the brain. The application of PD1-blocking antibody reduced tau hyperphosphorylation and GSK3β activity and prevented memory impairments. Mechanistically, we identified PD1 as a critical regulator of GSK3β activity. These results suggest that the immune regulation of the PD1/PDL1 axis is closely involved in AD.

Cannabis sativa L. oil extract affects neuroinflammation, clinical score, and cannabinoid receptor-1 gene expression in C57bl/6 experimental autoimmune encephalomyelitis

Introduction: Multiple sclerosis (MS) is a degenerative central nervous system disease derived by immune mechanisms, which ultimately results in clinical debilities. Numerous nutraceuticals have been cited to be effective in treatment of central nervous system complications. Objectives: This study investigated the effect of Cannabis sativa L. seed oil on experimental autoimmune encephalomyelitis (EAE). Materials and Methods: Female C57bl/6 mice were assigned randomly into three groups (8 in each). Group-A received no myelin oligodendrocyte glycoprotein (MOG), group B was immunized by MOG and treated with oil, while in group C animals were immunized and treated with normal saline. Clinical scores were recorded every other day throughout the study and after four weeks, all mice were sacrificed and spinal cords were incised for molecular and histopathological evaluations. Results: Significant differences were observed in mean clinical scores between control and experiment groups (P<0.001). Cannabinoid receptor-1 gene expression increased significantly in treatment group (P<0.001). Histopathologic evaluations also showed a significant decrease in overall infiltrated and vacuolated area and immune cells infiltration into the central nervous system in the treatment group (P<0.01). Conclusion: Cannabis sativa L. oil extract administration alleviated inflammation and paralysis in animal model. Therefore, its oil extract might be useful in soothing inflammatory and auto-immune diseases. However, additional research might be required.

Long non-coding RNA SNHG1 mediates neuronal damage in Parkinson's disease model cells by regulating miR-216a-3p/Bcl-2-associated X protein.

BackgroundParkinson’s disease (PD) is a common central nervous system degenerative disease in middle-aged and elderly people. Our study aimed to illuminate the relationship and mechanism of long-chain non-coding RNA SNHG1 and miRNA (miR)-216a-3p in PD.MethodsHuman neuroblastoma cell lines were treated with MPP+ to construct a PD model. Real-time fluorescent quantitative PCR was used to detect the cellular expression of SNHG1. Neuronal cell activity and apoptosis were compared before and after SNHG1 knock-down, as was neuronal miR-216a-3p expression. Further, a luciferase reporter gene experiment was performed to verify BAX as the target of miR-216a-3p. Anti-miR-216a-3p and BAX were co-transfected into PD model cells, and neuronal cellular activity and apoptosis were observed. Finally, the potential regulatory network of SNHG1/miR-216a-3p/BAX in PD was investigated.ResultsThe expression of miR-216a-3p was decreased in the PD model cells, and re-expression reversed the high apoptotic rate and cell vitality inhibition in PD model cells. SNHG1 interacted with miR-216a-3p and negatively regulated its upstream molecules, while miR-216a-3p attenuated the effect of SNHG1 knock-down on neurons. The overexpression of BAX in the PD cell model blocked the damage by miR-216a-3p to neurons. At the same time, SNHG1 acted as a coordinator, mediating the regulation of BAX via miR-216a-3p, thereby affecting the activity and apoptotic rate of neurons in the PD model.ConclusionsSNHG1 interacts with miR-216a-3p to regulate the expression of BAX. This SNHG1/miR-216a-3p/BAX molecular regulatory network is implicated in the pathogenesis of PD.

Protective effects of resveratrol liposomes on mitochondria in substantia nigra cells of parkinsonized rats

Parkinson's disease (PD) is a central nervous system degenerative disease. The progressive death of dopaminergic neurons is closely correlated to mitochondrial dysfunction. Resveratrol contains three hydroxyl groups, and has a strong neuroprotective effect. This study aimed to investigate the protective effect of resveratrol liposome on mitochondria of substantia nigra cells in Parkinsonized rats through experiment. The investigators used 6-hydroxydopamine to establish the Parkinsonized rat model, and used resveratrol liposome from Polygonum cuspidatum (20 mg·kg-1) for gavage, up to a total volume of 1 mL, once-daily, for two weeks. After treatment, the levels of mitochondrial membrane potential, mitochondrial complexes I-IV, mitochondrial cytochrome C, apoptosis-inducing factor (AIF), PTEN-induced putative kinase 1 (PINK1), tumor necrosis factor-receptor-associated protein 1 (TRAP1) and phosphorylated TRAP1 in rat mesencephalic cells were detected according to the operation instructions of the kits. After two weeks of treatment, resveratrol liposomes could significantly enhance the activity of mitochondrial electron transfer chain complex I in the substantia nigra cells of Parkinsonized model rats, promote the expression of complex I subcomponent MT-ND1-37kD, improve mitochondrial membrane potential, inhibit the release of mitochondrial cytochrome C and apoptotic inducible factor, enhance the expression of mitochondrial functional protein PINK1, increase the phosphorylated TRAP1 level, and elevate the phosphorylated TRAP1/TRAP1 ratio. Resveratrol liposome has positive effects on mitochondria in substantia nigra cells of Parkinsonized rats, and may be one of its pharmacological mechanisms.

The renin-angiotensin system in central nervous system tumors and degenerative diseases.

Despite their differences, central nervous system (CNS) tumors and degenerative diseases share important molecular mechanisms underlying their pathologies, due to their common anatomy. Here we review the role of the renin-angiotensin system (RAS) in CNS tumors and degenerative diseases, to highlight common molecular features and examine the potential merits in repurposing drugs that inhibit the RAS, its bypass loops, and converging signaling pathways. The RAS consists of key components, including angiotensinogen, (pro)renin receptor (PRR), angiotensin-converting enzyme 1 (ACE1), angiotensin-converting enzyme 2 (ACE2), angiotensin I (ATI), angiotensin II (ATII), ATII receptor 1 (AT1R), ATII receptor 2 (AT2R) and the Mas receptor (MasR). The RAS is integral to systemic and cellular pathways that regulate blood pressure and body fluid equilibrium and cellular homeostasis. The main effector of the RAS is ATII which exerts its effect by binding to AT1R and AT2R through two competitive arms: an ACE1/ATII/AT1R axis, which is involved in regulating oxidative stress and neuroinflammation pathways, and an ATII/AT2R and/or ATII/ACE2/Ang(1-7)/MasR axis that potentiates neuroprotection pathways. Alterations of these axes are associated with cellular dysfunction linked to CNS diseases. The generation of ATII is also influenced by proteases that constitute bypass loops of the RAS. These bypass loops include cathepsins B, D and G and chymase and aminopeptidases. The RAS is also influenced by converging pathways such as the Wnt/β-catenin pathway which sits upstream of the RAS via PRR, a key component of the RAS. We also discuss the co-expression of components of the RAS and markers of pluripotency, such as OCT4 and SOX2, in Parkinson's disease and glioblastoma, and their potential influences on transduction pathways involving the Wnt/β-catenin, MAPK/ERK, PI3K/AKT and vacuolar (H+) adenosine triphosphatase (V-ATPase) signaling cascades. Further research investigating modulation of the ACE1/ATII/AT1R and ACE2/Ang(1-7)/MasR axes with RAS inhibitors may lead to novel treatment of CNS tumors and degenerative diseases. The aim of this review article is to discuss and highlight experimental and epidemiological evidence for the role of the RAS, its bypass loops and convergent signaling pathways in the pathogenesis of CNS tumors and degenerative diseases, to direct research that may lead to the development of novel therapy.

Dendrobium nobile Lindl alkaloid attenuates 6-OHDA-induced dopamine neurotoxicity.

Parkinson's disease (PD) is one of the most common central nervous system (CNS) degenerative disease and is characterized by a progressive loss of midbrain substantia nigra dopamine (DA) neurons. Dendrobium nobileLindl alkaloid (DNLA) is an active component extracted from D. nobile Lindl, which is a traditional Chinese herb. The various pharmacological effects of D. nobile are beneficial for human health. Recently, DNLA-mediated neuroprotective effects have been reported. However, the neuroprotection of DNLA on 6-hydroxydopamine (6-OHDA)-induced DA neurotoxicity is still unknown. This study aimed to explore the neuroprotective effects of DNLA on DA neurotoxicity induced by 6-OHDA. In PD rat model, continuous intragastric administration of DNLA (20mg/kg) for 7 days significantly ameliorated 6-OHDA-induced DA neurons loss in the midbrain substantia nigra. In addition, primary rat midbrain neuron-glia cocultures were used to explore the mechanisms underlying DNLA-related DA neuroprotection. The studies on neuron-glia cocultures revealed that neuroprotective effects of DNLA (2.5ng/mL) were mediated by inhibiting the release of proinflammatory cytokines. Taken together, DNLA holds neuroprotective effect on 6-OHDA-induced neurons neurodegeneration by selectively inhibiting the production of proinflammatory factors and could be a potential compound for PD treatment.

The Role of Natural Compounds and their Nanocarriers in the Treatment of CNS Inflammation.

Neuroinflammation, which is involved in various inflammatory cascades in nervous tissues, can result in persistent and chronic apoptotic neuronal cell death and programmed cell death, triggering various degenerative disorders of the central nervous system (CNS). The neuroprotective effects of natural compounds against neuroinflammation are mainly mediated by their antioxidant, anti-inflammatory, and antiapoptotic properties that specifically promote or inhibit various molecular signal transduction pathways. However, natural compounds have several limitations, such as their pharmacokinetic properties and stability, which hinder their clinical development and use as medicines. This review discusses the molecular mechanisms of neuroinflammation and degenerative diseases of CNS. In addition, it emphasizes potential natural compounds and their promising nanocarriers for overcoming their limitations in the treatment of neuroinflammation. Moreover, recent promising CNS inflammation-targeted nanocarrier systems implementing lesion site-specific active targeting strategies for CNS inflammation are also discussed.

LncRNA NR_030777 Alleviates Paraquat-Induced Neurotoxicity by Regulating Zfp326 and Cpne5.

Paraquat (PQ) is herbicide widely used in agricultural production. It is identified as an environmental toxicant that could lead to neurodegeneration damage. Parkinson's disease (PD) is a central nervous system degenerative disease that occurs in the elderly. Main risk factors for PD include genetic and environmental variables, but its specific mechanism is still not well understood. Emerging evidence suggests that long noncoding RNAs (lncRNAs) play an important role in PD. LncRNA NR_030777 has a full length of 2208 bp and is highly conserved among species. RNA profiling showed a significant alteration in lncRNA NR_030777 expression upon PQ-induced neurotoxicity. However, little is known on the functional relevance of lncRNA NR_030777 in the development of PQ. In this study, we discovered a vital protective role of lncRNA NR_030777 in PQ-induced neurotoxicity. The expression of NR_030777 correlates with elevated level of reactive oxygen species induced by PQ. In addition, activated expression of NR_030777 alleviates neurotoxicity by regulating the expression of Zfp326 and Copine 5. We report that lncRNA NR_030777 has a vital protective role in neurotoxicity induced by environmental toxicants such as PQ. This study could serve as an exemplary case for lncRNAs to be considered as a potential target for the prevention and treatment of PQ-induced neurodegenerative disorders such as PD.

Vesicular Transport of Encapsulated microRNA between Glial and Neuronal Cells.

Exosomes (EXs) and extracellular microvesicles (EMVs) represent a diverse assortment of plasma membrane-derived nanovesicles, 30–1000 nm in diameter, released by all cell lineages of the central nervous system (CNS). They are examples of a very active and dynamic form of extracellular communication and the conveyance of biological information transfer essential to maintain homeostatic neurological functions and contain complex molecular cargoes representative of the cytoplasm of their cells of origin. These molecular cargoes include various mixtures of proteins, lipids, proteolipids, cytokines, chemokines, carbohydrates, microRNAs (miRNA) and messenger RNAs (mRNA) and other components, including end-stage neurotoxic and pathogenic metabolic products, such as amyloid beta (Aβ) peptides. Brain microglia, for example, respond to both acute CNS injuries and degenerative diseases with complex reactions via the induction of a pro-inflammatory phenotype, and secrete EXs and EMVs enriched in selective pathogenic microRNAs (miRNAs) such as miRNA-34a, miRNA-125b, miRNA-146a, miRNA-155, and others that are known to promote neuro-inflammation, induce complement activation, disrupt innate–immune signaling and deregulate the expression of neuron-specific phosphoproteins involved in neurotropism and synaptic signaling. This communication will review our current understanding of the trafficking of miRNA-containing EXs and EMVs from astrocytes and “activated pro-inflammatory” microglia to target neurons in neurodegenerative diseases with an emphasis on Alzheimer’s disease wherever possible.

Ellagic acid protects dopamine neurons from rotenone-induced neurotoxicity via activation of Nrf2 signalling.

Parkinson's disease (PD) is the second most prevalent central nervous system (CNS) degenerative disease. Oxidative stress is one of key contributors to PD. Nuclear factor erythroid‐2‐related factor 2 (Nrf2) is considered to be a master regulator of many genes involved in anti‐oxidant stress to attenuate cell death. Therefore, activation of Nrf2 signalling provides an effective avenue to treat PD. Ellagic acid (EA), a natural polyphenolic contained in fruits and nuts, possesses amounts of pharmacological activities, such as anti‐oxidant stress and anti‐inflammation. Recent studies have confirmed EA could be used as a neuroprotective agent in neurodegenerative diseases. Here, mice subcutaneous injection of rotenone (ROT)‐induced DA neuronal damage was performed to investigate EA‐mediated neuroprotection. In addition, adult Nrf2 knockout mice and different cell cultures including MN9D‐enciched, MN9D‐BV‐2 and MN9D‐C6 cell co‐cultures were applied to explore the underlying mechanisms. Results demonstrated EA conferred neuroprotection against ROT‐induced DA neurotoxicity. Activation of Nrf2 signalling was involved in EA‐mediated DA neuroprotection, as evidenced by the following observations. First, EA activated Nrf2 signalling in ROT‐induced DA neuronal damage. Second, EA generated neuroprotection with the presence of astroglia and silence of Nrf2 in astroglia abolished EA‐mediated neuroprotection. Third, EA failed to produce DA neuroprotection in Nrf2 knockout mice. In conclusion, this study identified EA protected against DA neuronal loss via an Nrf2‐dependent manner.

MicroRNA-203a-3p Regulates the Apoptosis of MPP+ Induced SH-SY5Y Cells by Targeting A-Synuclein

Parkinson's disease (PD) is a universal central nervous system degenerative diseases and has a serious impact on people's lives. MicroRNA-203a-3p (miR-203a-3p) is a tumor-inhibiting factor. Nevertheless, the role and mechanism of miR-203a-3p in PD remain unclear. Therefore, this investigated the role and underlying mechanism of miR-203a-3p in PD. Firstly, we have established a PD cell model by treating SH-SY5Y cells with MMP+. We found that cell viability gradually decreased with increased MMP+ concentration. Subsequently, we choose 2000 μM MMP+ for subsequent experiments. Then, qRT-PCR assay demonstrated that miR-203a-3p was down-regulated in MMP+ treated SH-SY5Y cells. Next, results from TargetScan and dual luciferase reporter gene assay suggested that a-synuclein (SNCA), an important genetic risk factor of PD, had direct binding sites with miR-203a-3p. Subsequently, we confirmed that miR-203a-3p negatively regulated SNCA expression in SH-SY5Y cells. Finally, we investigated the influence of miR-203a-3p on MMP+ -induced SH-SY5Y cells. CCK-8 assay results showed that MMP + reduced cell proliferation and induced apoptosis were inhibited by miR-203a-3p up-regulation. In addition, we found that MMP+ enhanced expression of SNCA, p53 and cleaved Caspase-3 proteins was reduced by miR-203a-3p overexpression. However, these changes were reversed by SNCA-plasmid. In conclusion, miR-203a-3p regulated the apoptosis of MPP+ induced SH-SY5Y cells by targeting SNCA. miR-203a-3p/SNCA axis might be a new latent targets for PD therapy.

Core cell cycle machinery is crucially involved in both life and death of post-mitotic neurons.

A persistent dogma in neuroscience supported the idea that terminally differentiated neurons permanently withdraw from the cell cycle. However, since the late 1990s, several studies have shown that cell cycle proteins are expressed in post-mitotic neurons under physiological conditions, indicating that the cell cycle machinery is not restricted to proliferating cells. Moreover, many studies have highlighted a clear link between cell cycle-related proteins and neurological disorders, particularly relating to apoptosis-induced neuronal death. Indeed, cell cycle-related proteins can be upregulated or overactivated in post-mitotic neurons in case of acute or degenerative central nervous system disease. Given the considerable lack of effective treatments for age-related neurological disorders, new therapeutic approaches targeting the cell cycle machinery might thus be considered. This review aims at summarizing current knowledge about the role of the cell cycle machinery in post-mitotic neurons in healthy and pathological conditions.

Hydrogen Sulfide and Endoplasmic Reticulum Stress: A Potential Therapeutic Target for Central Nervous System Degeneration Diseases.

There are three members of the endogenous gas transmitter family. The first two are nitric oxide and carbon monoxide, and the third newly added member is hydrogen sulfide (H2S). They all have similar functions: relaxing blood vessels, smoothing muscles, and getting involved in the regulation of neuronal excitation, learning, and memory. The cystathionine β-synthase (CBS), 3-mercaptopyruvate sulfur transferase acts together with cysteine aminotransferase (3-MST/CAT), cystathionine γ-lyase (CSE), and 3-mercaptopyruvate sulfur transferase with D-amino acid oxidase (3-MST/DAO) pathways are involved in the enzymatic production of H2S. More and more researches focus on the role of H2S in the central nervous system (CNS), and H2S plays a significant function in neuroprotection processes, regulating the function of the nervous system as a signaling molecule in the CNS. Endoplasmic reticulum stress (ERS) and protein misfolding in its mechanism are related to neurodegenerative diseases. H2S exhibits a wide variety of cytoprotective and physiological functions in the CNS degenerative diseases by regulating ERS. This review summarized on the neuroprotective effect of H2S for ERS played in several CNS diseases including Alzheimer’s disease, Parkinson’s disease, and depression disorder, and discussed the corresponding possible signaling pathways or mechanisms as well.