Displaying publications 1 - 20 of 31 in total

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  1. Role of α7 nicotinic acetylcholine receptor subtype in neuroprotection: an overview
    Muthuraju, S., Abdullah, J.M.
    Orient Neuron Nexus, 2011;2(1):10-14.
    MyJurnal
    Neuronal cell death results from various circumstances such as hypoxia, ischemic and neurodegenerative diseases (NDs). In these events, the resulting modification of neurotransmitters, either excitatory or inhibitory, mediate much of the neuronal damage. However, this consequence depends upon their pre and post synaptic receptor activities which are the key mechanism for signal regulation. Among these, acetylcholine (ACh) is a well known neurotransmitter which is predominantly involved in neuroprotection as well as cognitive functions through its receptors activity, particularly the nicotinic subtypes. Several lines of evidence suggest that among these subtypes, a7 nicotinic acetylcholine receptor (a7nAChR) offers much promise for neuroprotective role in relation to the central nervous system (CNS) disorders like schizophrenia and Alzheimer's disease (AD). Several lines of evidence exist to show the potential mechanisms in which this nAChR subtype and its agonists such as nicotine, that trigger the a7nAChR-mediated suppression of neuronal cell death. This review focuses on the potential role of a7nAChR in neuroprotection by examining recent experimental data, both in vitro and in vivo, that argue for the neuroprotective role of a7nAChR in the CNS.
    Matched MeSH terms: Neuroprotection
  2. Glutamate receptors and transporters as comparative cues to the glutamatergic circuits of the avian and mammalian brain
    Islam, M.R., Muzaimi, M., Abdullah, J.M.
    Orient Neuron Nexus, 2011;2(1):2-9.
    MyJurnal
    Glutamate is the principal excitatory neurotransmitter in the central nervous system, and plays important roles in both physiological and pathological neuronal processes. Current understanding of the exact mechanisms involved in glutamate-induced neuronal excitotoxicity, in which excessive glutamate causes neuronal dysfunction and degeneration, whether acute or chronic, remain elusive. Conditions, due to acute insults such as ischaemia and traumatic brain injury, and chronic neurodegenerative disorders such as multiple sclerosis and motor neuron disease, suffer from the lack of translational neuroprotection in clinical setting to tackle glutamate excitotoxicity despite steady growth of animal studies that revealed complex cell death pathway interactions. In addition, glutamates are also released by non-neuronal cells including astrocytes and oligodendroglia. Thus, attempts to elucidate this complexity are closely related to our understanding of the glutamatergic circuitry in the brain. Neuronal cells develop a glutamatergic system at glutamatergic synapses that utilise glutamate as an intercellular signaling molecule to characterise the output, input, and termination of this signaling. As to signal input, various kinds of glutamate receptors have been identified and characterized. Na+-dependent glutamate transporters at the plasma membrane are responsible for the signal termination through sequestration of glutamate from the synaptic cleft. The signal output systems comprise vesicular storage and subsequent exocytosis of glutamate by using vesicular glutamate transporters. Similar to the mammalian brain, the regional differences of glutamatergic neurons and glutamate receptor neurons suggest many glutamatergic projections in the avian brain, as supported by recent evidence of glutamate-related genes distribution. Glutamatergic target areas are expected to show high activity of glutamate transporters that remove released glutamate from the synaptic clefts. This review summarises and compares glutamatergic circuits in the avian and mammalian brain, particularly in the olfactory pathway, the paffial organization of glutamatergic neurons and connection with the striatum, hippocampal-septal pathway, visual and auditory pathways, and granule cell-Purkinje cell pathway in the cerebellum. Comparative appreciation of these glutamatergic circuits, particularly with the localisation and/or expression of specific subtypes of glutamate transporters, would provide the morphological basis for physiological and pharmacological designs that supplement existing animal studies of the current proposed mechanisms that underlie glutamate-induced neuronal excitotoxicity.
    Matched MeSH terms: Neuroprotection
  3. Fulltext Ethnobotanical, Phytochemical, Pharmacological, and Toxicological Aspects of Persicaria hydropiper (L.) Delarbre
    Huq AK, Jamal JA, Stanslas J
    Evid Based Complement Alternat Med, 2014;2014:782830.
    PMID: 24834098 DOI: 10.1155/2014/782830
    Persicaria hydropiper (L.) Delarbre, belonging to Polygonaceae family, is a common weed found in most of the temperate countries including Bangladesh, China, Malaysia, and Japan. The plant is also referred to as "marsh pepper" or "smart weed." It appears to be a useful herb with evidence-based medicinal properties. The present work addresses the botanical description, traditional uses, phytochemistry, pharmacology, and toxicology of P. hydropiper. All plant parts have been commonly used in the traditional systems of medicines. Flavonoids are the major group of phytochemical components followed by drimane-type sesquiterpenes and sesquiterpenoids, as well as phenylpropanoids. Different extracts and plant parts showed remarkable pharmacological activities including antioxidant, antibacterial, antifungal, antihelminth, antifeedant, cytotoxicity, anti-inflammatory, antinociceptive, oestrogenicity, antifertility, antiadipogenicity, and neuroprotection. Mutagenicity and acute and subchronic toxicities of the plant were also reported. P. hydropiper has tremendous medicinal properties that could further be investigated for the development of evidence-based herbal products.
    Matched MeSH terms: Neuroprotection
  4. A Molecular Approach to Epilepsy Management: from Current Therapeutic Methods to Preconditioning Efforts
    Amini E, Rezaei M, Mohamed Ibrahim N, Golpich M, Ghasemi R, Mohamed Z, et al.
    Mol Neurobiol, 2015 Aug;52(1):492-513.
    PMID: 25195699 DOI: 10.1007/s12035-014-8876-5
    Epilepsy is the most common and chronic neurological disorder characterized by recurrent unprovoked seizures. The key aim in treating patients with epilepsy is the suppression of seizures. An understanding of focal changes that are involved in epileptogenesis may therefore provide novel approaches for optimal treatment of the seizure. Although the actual pathogenesis of epilepsy is still uncertain, recently growing lines of evidence declare that microglia and astrocyte activation, oxidative stress and reactive oxygen species (ROS) production, mitochondria dysfunction, and damage of blood-brain barrier (BBB) are involved in its pathogenesis. Impaired GABAergic function in the brain is probably the most accepted hypothesis regarding the pathogenesis of epilepsy. Clinical neuroimaging of patients and experimental modeling have demonstrated that seizures may induce neuronal apoptosis. Apoptosis signaling pathways are involved in the pathogenesis of several types of epilepsy such as temporal lobe epilepsy (TLE). The quality of life of patients is seriously affected by treatment-related problems and also by unpredictability of epileptic seizures. Moreover, the available antiepileptic drugs (AED) are not significantly effective to prevent epileptogenesis. Thus, novel therapies that are proficient to control seizure in people who are suffering from epilepsy are needed. The preconditioning method promises to serve as an alternative therapeutic approach because this strategy has demonstrated the capability to curtail epileptogenesis. For this reason, understanding of molecular mechanisms underlying brain tolerance induced by preconditioning is crucial to delineate new neuroprotective ways against seizure damage and epileptogenesis. In this review, we summarize the work to date on the pathogenesis of epilepsy and discuss recent therapeutic strategies in the treatment of epilepsy. We will highlight that novel therapy targeting such as preconditioning process holds great promise. In addition, we will also highlight the role of gene reprogramming and mitochondrial biogenesis in the preconditioning-mediated neuroprotective events.
    Matched MeSH terms: Neuroprotection*
  5. Fulltext Kainic Acid-Induced Excitotoxicity Experimental Model: Protective Merits of Natural Products and Plant Extracts
    Mohd Sairazi NS, Sirajudeen KN, Asari MA, Muzaimi M, Mummedy S, Sulaiman SA
    Evid Based Complement Alternat Med, 2015;2015:972623.
    PMID: 26793262 DOI: 10.1155/2015/972623
    Excitotoxicity is well recognized as a major pathological process of neuronal death in neurodegenerative diseases involving the central nervous system (CNS). In the animal models of neurodegeneration, excitotoxicity is commonly induced experimentally by chemical convulsants, particularly kainic acid (KA). KA-induced excitotoxicity in rodent models has been shown to result in seizures, behavioral changes, oxidative stress, glial activation, inflammatory mediator production, endoplasmic reticulum stress, mitochondrial dysfunction, and selective neurodegeneration in the brain upon KA administration. Recently, there is an emerging trend to search for natural sources to combat against excitotoxicity-associated neurodegenerative diseases. Natural products and plant extracts had attracted a considerable amount of attention because of their reported beneficial effects on the CNS, particularly their neuroprotective effect against excitotoxicity. They provide significant reduction and/or protection against the development and progression of acute and chronic neurodegeneration. This indicates that natural products and plants extracts may be useful in protecting against excitotoxicity-associated neurodegeneration. Thus, targeting of multiple pathways simultaneously may be the strategy to maximize the neuroprotection effect. This review summarizes the mechanisms involved in KA-induced excitotoxicity and attempts to collate the various researches related to the protective effect of natural products and plant extracts in the KA model of neurodegeneration.
    Matched MeSH terms: Neuroprotection
  6. Fulltext Recent Updates in Neuroprotective and Neuroregenerative Potential of Centella asiatica
    Lokanathan Y, Omar N, Ahmad Puzi NN, Saim A, Hj Idrus R
    Malays J Med Sci, 2016 Jan;23(1):4-14.
    PMID: 27540320 MyJurnal
    Centella asiatica, locally well known in Malaysia as pegaga, is a traditional herb that has been used widely in Ayurvedic medicine, traditional Chinese medicine, and in the traditional medicine of other Southeast Asian countries including Malaysia. Although consumption of the plant is indicated for various illnesses, its potential neuroprotective properties have been well studied and documented. In addition to past studies, recent studies also discovered and/or reconfirmed that C. asiatica acts as an antioxidant, reducing the effect of oxidative stress in vitro and in vivo. At the in vitro level, C. asiatica promotes dendrite arborisation and elongation, and also protects the neurons from apoptosis. In vivo studies have shown that the whole extract and also individual compounds of C. asiatica have a protective effect against various neurological diseases. Most of the in vivo studies on neuroprotective effects have focused on Alzheimer's disease, Parkinson's disease, learning and memory enhancement, neurotoxicity and other mental illnesses such as depression and anxiety, and epilepsy. Recent studies have embarked on finding the molecular mechanism of neuroprotection by C. asiatica extract. However, the capability of C. asiatica in enhancing neuroregeneration has not been studied much and is limited to the regeneration of crushed sciatic nerves and protection from neuronal injury in hypoxia conditions. More studies are still needed to identify the compounds and the mechanism of action of C. asiatica that are particularly involved in neuroprotection and neuroregeneration. Furthermore, the extraction method, biochemical profile and dosage information of the C. asiatica extract need to be standardised to enhance the economic value of this traditional herb and to accelerate the entry of C. asiatica extracts into modern medicine.
    Matched MeSH terms: Neuroprotection
  7. Fulltext Stem cell therapy as a potential treatment for glaucoma
    Kamal, M., Amini, F., Ramasamy, TS
    JUMMEC, 2016;19(1):23-32.
    MyJurnal
    Glaucoma is a common eye disease that can cause irreversible damage if left undiagnosed and untreated. It is one of the most common neurodegenerative diseases causing blindness. Pre-clinical studies have been carried out on animal models of glaucoma for stem cell therapy. We carried out a systematic review to determine whether stem cell therapy had the potential to treat glaucoma. Nine studies were selected based on the predetermined inclusion and exclusion criteria. Of these nine studies, eight focused on neuroprotection conferred by stem cells, and the remaining one on neuroregeneration. Results from these studies showed that there was a potential in stem cell based therapy in treating glaucoma, especially regarding neuroprotection via neurotrophic factors. The studies revealed that a brain-derived neurotrophic factor expressed by stem cells promoted the survival of retinal ganglion cells in murine glaucoma models. The transplanted cells survived without any side effects. While these studies proved that stem cells provided neuroprotection in glaucoma, improvement of vision could not be determined. Clinical studies would be required to determine whether the protection of RGC correlated with improvement in visual function. Furthermore, these murine studies could not be translated into clinical therapy due to the heterogeneity of the experimental methods and the
    use of different cell lines. In conclusion, the use of stem cells in the clinical therapy of glaucoma will be an important step in the future as it will transform present-day treatment with the hope of restoring sight to patients with glaucoma.
    Matched MeSH terms: Neuroprotection
  8. Ischemic optic neuropathy as a model of neurodegenerative disorder: A review of pathogenic mechanism of axonal degeneration and the role of neuroprotection
    Khalilpour S, Latifi S, Behnammanesh G, Majid AM, Majid AS, Tamayol A
    J Neurol Sci, 2017 Apr 15;375:430-441.
    PMID: 28320183 DOI: 10.1016/j.jns.2016.12.044
    Optic neuropathy is a neurodegenerative disease which involves optic nerve injury. It is caused by acute or intermittent insults leading to visual dysfunction. There are number of factors, responsible for optic neuropathy, and the optic nerve axon is affected in all type which causes the loss of retinal ganglion cells. In this review we will highlight various mechanisms involved in the cell loss cascades during axonal degeneration as well as ischemic optic neuropathy. These mechanisms include oxidative stress, excitotoxicity, angiogenesis, neuroinflammation and apoptosis following retinal ischemia. We will also discuss the effect of neuroprotective agents in attenuation of the negative effect of factors involve in the disease occurrence and progression.
    Matched MeSH terms: Neuroprotection/physiology*
  9. Fulltext A status review of the bioactive activities of tiger milk mushroom Lignosus rhinocerotis (Cooke) Ryvarden
    Nallathamby N, Phan CW, Seow SL, Baskaran A, Lakshmanan H, Abd Malek SN, et al.
    Front Pharmacol, 2017;8:998.
    PMID: 29379443 DOI: 10.3389/fphar.2017.00998
    Edible and medicinal mushrooms are regularly used in natural medicines and home remedies since antiquity for ailments like fever, inflammation, and respiratory disorders. Lignosus rhinocerotis (Cooke) Ryvarden is a polypore found in Malaysia and other regions in South East Asia. It can be located on a spot where a tigress drips milk while feeding, hence the name "tiger's milk mushroom." The sclerotium of L. rhinocerotis is highly sought after by the native communities in Malaysia to stave off hunger, relieve cough and asthma, and provide stamina. The genomic features of L. rhinocerotis have been described. The pharmacological and toxicity effects, if any, of L. rhinocerotis sclerotium have been scientifically verified in recent years. In this review, the validated investigations including the cognitive function, neuroprotection, immune modulation, anti-asthmatic, anti-coagulation, anti-inflammatory, anti-microbial/ anti-viral, anti-obesity, anti-cancer/ anti-tumor, and antioxidant properties are highlighted. These findings suggest that L. rhinocerotis can be considered as an alternative and natural medicine in the management of non-communicable diseases. However, there is a paucity of validation studies including human clinical trials of the mycochemicals of L. rhinocerotis.
    Matched MeSH terms: Neuroprotection
  10. C-Abl Inhibition; A Novel Therapeutic Target for Parkinson's Disease
    Abushouk AI, Negida A, Elshenawy RA, Zein H, Hammad AM, Menshawy A, et al.
    CNS Neurol Disord Drug Targets, 2018 Apr 26;17(1):14-21.
    PMID: 28571531 DOI: 10.2174/1871527316666170602101538
    Parkinson's disease (PD) is the most prevalent movement disorder in the world. The major pathological hallmarks of PD are death of dopaminergic neurons and the formation of Lewy bodies. At the moment, there is no cure for PD; current treatments are symptomatic. Investigators are searching for neuroprotective agents and disease modifying strategies to slow the progress of neurodegeneration. However, due to lack of data about the main pathological sequence of PD, many drug targets failed to provide neuroprotective effects in human trials. Recent evidence suggests the involvement of C-Abelson (c-Abl) tyrosine kinase enzyme in the pathogenesis of PD. Through parkin inactivation, alpha synuclein aggregation, and impaired autophagy of toxic elements. Experimental studies showed that (1) c-Abl activation is involved in neurodegeneration and (2) c-Abl inhibition shows neuroprotective effects and prevents dopaminergic neuronal' death. Current evidence from experimental studies and the first in-human trial shows that c-Abl inhibition holds the promise for neuroprotection against PD and therefore, justifies the movement towards larger clinical trials. In this review article, we discussed the role of c-Abl in PD pathogenesis and the findings of preclinical experiments and the first in-human trial. In addition, based on lessons from the last decade and current preclinical evidence, we provide recommendations for future research in this area.
    Matched MeSH terms: Neuroprotection
  11. Fulltext A brief review of potential neuroprotective roles of the culinary herb Ocimum basilicum
    Manali Haniti, M.Z., Norazrina, A., Chan, K.M.
    Medicine & Health, 2018;13(2):3-19.
    MyJurnal
    Neurodegenerative diseases commonly affect elderly population and are characterised by progressive neuronal loss. Oxidative stress is highly associated with neurodegeneration. The targeted herbal plant in this review, Ocimum basilicum (O. basilicum), is typically used in Indochina and Italian cuisine. Pharmacological studies on O. basilicum have demonstrated potent antioxidant activities with some reports of neuroprotective actions. This brief review highlights the potential neuroprotective roles of O. basilicum by discussing previously documented antioxidative actions of the plant extract, essential oils and its phytochemical compounds on the nervous system based on in vitro and in vivo studies. Accumulating evidence on the neuroprotective action of O. basilicum points to a notion that neuroprotection is made possible by way of its antioxidant properties and largely due to the presence of polyphenol compounds such as rosmarinic acid which has been identified as the major constituent. Although the mechanisms of O. basilicum antioxidant action have been proposed, further studies are required for better understanding of its antioxidant action leading to neuroprotective roles. It is also possible that the antioxidant actions of O. basilicum are mediated through synergism of a mixture of various naturally-occurring bioactive compounds in the plant, as is with many other plant-based food supplements, to produce the putative effects instead of a single bioactive compound from the plant. Therefore, specific targeting of neuroprotection by means of antioxidant actions warrants further preclinical and clinical studies investigating the therapeutic potentials of O. basilicum particularly in view of the prevention of neurodegenerative processes.
    Matched MeSH terms: Neuroprotection
  12. Fulltext Brain Lipopolysaccharide Preconditioning-Induced Gene Reprogramming Mediates a Tolerance State in Electroconvulsive Shock Model of Epilepsy
    Amini E, Golpich M, Farjam AS, Kamalidehghan B, Mohamed Z, Ibrahim NM, et al.
    Front Pharmacol, 2018;9:416.
    PMID: 29765321 DOI: 10.3389/fphar.2018.00416
    There is increasing evidence pointing toward the role of inflammatory processes in epileptic seizures, and reciprocally, prolonged seizures induce more inflammation in the brain. In this regard, effective strategies to control epilepsy resulting from neuroinflammation could be targeted. Based on the available data, preconditioning (PC) with low dose lipopolysaccharide (LPS) through the regulation of the TLR4 signaling pathway provides neuroprotection against subsequent challenge with injury in the brain. To test this, we examined the effects of a single and chronic brain LPS PC, which is expected to lead to reduction of inflammation against epileptic seizures induced by electroconvulsive shock (ECS). A total of 60 male Sprague Dawley rats were randomly assigned to five groups: control, vehicle (single and chronic), and LPS PC (single and chronic). We first recorded the data regarding the behavioral and histological changes. We further investigated the alterations of gene and protein expression of important mediators in relation to TLR4 and inflammatory signaling pathways. Interestingly, significant increased presence of NFκB inhibitors [Src homology 2-containing inositol phosphatase-1 (SHIP1) and Toll interacting protein (TOLLIP)] was observed in LPS-preconditioned animals. This result was also associated with over-expression of IRF3 activity and anti-inflammatory markers, along with down-regulation of pro-inflammatory mediators. Summarizing, the analysis revealed that PC with LPS prior to seizure induction may have a neuroprotective effect possibly by reprogramming the signaling response to injury.
    Matched MeSH terms: Neuroprotection
  13. Neuroprotection by Human Dental Pulp Mesenchymal Stem Cells: From Billions to Nano
    Venugopal C, K S, Rai KS, Pinnelli VB, Kutty BM, Dhanushkodi A
    Curr Gene Ther, 2018;18(5):307-323.
    PMID: 30209999 DOI: 10.2174/1566523218666180913152615
    INTRODUCTION: Mesenchymal Stem Cell (MSC) therapy in recent years has gained significant attention. Though the functional outcomes following MSC therapy for neurodegenerative diseases are convincing, various mechanisms for the functional recovery are being debated. Nevertheless, recent studies convincingly demonstrated that recovery following MSC therapy could be reiterated with MSC secretome per se thereby shifting the dogma from cell therapy to cell "based" therapy. In addition to various functional proteins, stem cell secretome also includes extracellular membrane vesicles like exosomes. Exosomes which are of "Nano" size have attracted significant interest as they can pass through the bloodbrain barrier far easily than macro size cells or growth factors. Exosomes act as a cargo between cells to bring about significant alterations in target cells. As the importance of exosomes is getting unveil, it is imperial to carry out a comprehensive study to evaluate the neuroprotective potential of exosomes as compared to conventional co-culture or total condition medium treatments.

    OBJECTIVE: Thus, the present study is designed to compare the neuroprotective potential of MSC derived exosomes with MSC-condition medium or neuron-MSC-co-culture system against kainic acid induced excitotoxicity in in vitro condition. The study also aims at comparing the neuroprotective efficacy of exosomes/condition medium/co-culture of two MSC viz., neural crest derived human Dental Pulp Stem Cells (hDPSC) and human Bone-Marrow Mesenchymal Stem Cells (hBM-MSC) to identify the appropriate MSC source for treating neurodegenerative diseases.

    RESULT: Our results demonstrated that neuroprotective efficacy of MSC-exosomes is as efficient as MSC-condition medium or neuron-MSC co-culture system and treating degenerating hippocampal neurons with all three MSC based approaches could up-regulate host's endogenous growth factor expressions and prevent apoptosis by activating cell survival PI3K-B-cell lymphoma-2 (Bcl-2) pathway.

    CONCLUSION: Thus, the current study highlights the possibilities of treating neurodegenerative diseases with "Nano" size exosomes as opposed to transplanting billions of stem cells which inherit several disadvantages.

    Matched MeSH terms: Neuroprotection*
  14. Fulltext Development and evaluation of acceptance of a web based education module for reducing risk of mild cognitive impairment among older adults
    Suzana Shahar, Divya Vanoh, Intan Hafizah Mohd Ishak, Zahara Abdul Manaf, Rosdinom Razali, Nazlena Mohd Ali, et al.
    Jurnal Sains Kesihatan Malaysia, 2018;16(101):233-234.
    MyJurnal
    Relatively less comprehensive web based programme has been developed for detecting risk of mild cognitive impairment (MCI) and further impart preventive strategies and lifestyle education. Thus, this study has developed a comprehensive web based programme for early screening of risk of MCI together with education package for preventing MCI known as WESIHAT 2.0. WESIHAT 2.0 is a senior friendly website which has appropriate design interface facilitating access of older people especially with the use of touch-screen technology. WESIHAT 2.0 has incorporated four major components namely TUA WELLNESS screening tool, which is a comprehensive, online based, 10-item screening tool for detecting risk of MCI, 10-guides for preventing MCI, health diary and healthy food. Evaluation of acceptance of WESIHAT 2.0 was done among 71 people which comprised of 30 older people and 30 caregivers, chosen equally based on ethnic composition and 11 health care professionals who has experience working in the field of geriatric and 2 freelance website developer. All older people and caregivers stated that the content of website was very useful for preventing MCI, however, about 36.4% of health professionals stated several improvements needed to be done before releasing the end-product to the users. Comments given were smaller font size (27.3), addition of more pictures (27.3%), using simpler terms (36.4%) and changing certain design for better view of older people (18.2%). Amendments were made based on each comment given and the finalized website were used for a 6-month intervention programme for neuroprotection among older people who failed to achieve successful aging. It is timely for an online based approach for prevention of MCI. WESIHAT 2.0 is the first website in Malaysia which has been accepted by all older people and caregiver and more than half of healthcare professionals to prevent memory decline.
    Matched MeSH terms: Neuroprotection
  15. The NLRP3 inflammasome is involved in the neuroprotective mechanism of neural stem cells against microglia-mediated toxicity in SH-SY5Y cells via the attenuation of tau hyperphosphorylation and amyloidogenesis
    Chan EWL, Krishnansamy S, Wong C, Gan SY
    Neurotoxicology, 2019 01;70:91-98.
    PMID: 30408495 DOI: 10.1016/j.neuro.2018.11.001
    The cognitive impairment caused by Alzheimer's disease (AD) is associated with beta-amyloid (Aβ) and tau proteins, and is accompanied by inflammation. Recently, a novel inflammasome signaling pathway has been uncovered. Inflammasomes are implicated in the execution of inflammatory responses and pyroptotic death leading to neurodegeneration. Thus, the inflammasome signaling pathway could be a potential therapeutic target for AD. Neural stem cells (NSCs) are multipotent cells that can self-renew and differentiate into distinct neural cells. NSC therapy has been considered to be a promising therapeutic approach in protecting the central nervous system and restoring it following damage. However, the mechanisms involved remain unclear. The aims of this study were to investigate the protective effects of NE4C neural stem cells against microglia-mediated neurotoxicity and to explore molecular mechanisms mediating their actions. NE4C decreased the levels of caspase-1 and IL-1β, and attenuated the level of the NLRP3 inflammasome and its associated protein adapter, apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain (ASC) in LPS-stimulated BV2 microglial cells, possibly by regulating the phosphorylation of p38α MAPK. The conditioned media obtained from co-culture of LPS-stimulated BV2 and NE4C cells exhibited protective effects on SH-SY5Y cells against microglia-mediated neurotoxicity; this was associated with an attenuation of tau phosphorylation and amyloidogenesis and accompanied by down-regulation of GSK-3β and p38α MAPK signalling pathways. In conclusion, the present study suggested that NSC therapy could be a potential strategy against microglia-mediated neurotoxicity. NSCs regulate NLRP3 activation and IL-1β secretion, which are critical in the initiation of the inflammatory responses, hence preventing the release of neurotoxic pro-inflammatory factors by microglia. This eventually reduces tau hyperphosphylation and amyloidogenesis, possibly through the regulation of GSK-3β and p38α MAPK signalling pathways, and thus protects SH-SY5Y cells against microglia-mediated neurotoxicity.
    Matched MeSH terms: Neuroprotection/drug effects; Neuroprotection/physiology*
  16. Fulltext Multi-targeting aurones with monoamine oxidase and amyloid-beta inhibitory activities: Structure-activity relationship and translating multi-potency to neuroprotection
    Liew KF, Lee EH, Chan KL, Lee CY
    Biomed Pharmacother, 2019 Feb;110:118-128.
    PMID: 30466001 DOI: 10.1016/j.biopha.2018.11.054
    Previously, a series of aurones bearing amine and carbamate functionalities was synthesized and evaluated for their cholinesterase inhibitory activity and drug-like attributes. In the present study, these aurones were evaluated for their multi-targeting properties in two Alzheimer's disease (AD)-related activities namely, monoamine oxidase (MAO) and amyloid-beta (Aβ) inhibition. Evaluation of the aurones for MAO inhibitory activity disclosed several potent selective inhibitors of MAO-B, particularly those with 6-methoxyl group attached at ring A. Of the different amine moieties attached as side chains, pyrrolidine-bearing aurones were prominent as represented by 2-2, the most potent inhibitor. Evaluation on the Aβ aggregation inhibition identified 4-3 as the best inhibitor with a percentage inhibition comparable to that of a known Aβ inhibitor curcumin. Examination on the neuroprotective ability of the more drug-like aurone 4-3 in two Caenorhabditis elegans neurodegeneration models showed 4-3 to protect the nematodes against both Aβ- and 6-hydroxydopamine-induced toxicities. These new activities further support 4-3 as a promising lead to develop the aurones as potential multipotent agents for neurodegenerative diseases.
    Matched MeSH terms: Neuroprotection/drug effects*; Neuroprotection/physiology
  17. Current viral-mediated gene transfer research for treatment of Alzheimer's disease
    Sasmita AO
    Biotechnol Genet Eng Rev, 2019 Apr;35(1):26-45.
    PMID: 30317930 DOI: 10.1080/02648725.2018.1523521
    Alzheimer's disease (AD) is the most common form of dementia and has affected millions of individuals worldwide. The hallmarks of AD include the amyloid beta plaque deposits, tau neurofibrillary tangles, altered neuronal signaling, alongside decline in memory and cognitive functions. Conventional drug therapies do exist, such as donepezil or aducanumab, but these drugs mostly focus on halting AD progression instead of causing a reversal within the disease. In an effort to ameliorate and ultimately cure AD, researchers have delved into viral-mediated gene therapy to fix this disease from its root molecular causes. To date, adeno-associated virus and lentiviral vectors have remained the most vastly studied among other viral vectors to combat AD. These vectors could be employed alongside various genetic materials based on the types of processes we want to alter to yield a positive effect, such as disruption of amyloidogenic pathway, neuroprotection and lipid metabolism pathways. Recent studies and trials were reviewed in this article, highlighting their clinical significance, differences and limitations between each method. By learning from the different combinations and possibilities of viral-mediated gene transfer, researchers would then get a step closer in ameliorating symptoms and possibly in curing AD.
    Matched MeSH terms: Neuroprotection
  18. miR-124 and Parkinson's disease: A biomarker with therapeutic potential
    Angelopoulou E, Paudel YN, Piperi C
    Pharmacol Res, 2019 12;150:104515.
    PMID: 31707035 DOI: 10.1016/j.phrs.2019.104515
    Parkinson's disease (PD) is a multifactorial disorder, attributed to a complex interplay between genetic and epigenetic factors. Although the exact etiology of the disease remains elusive, dysregulation of signaling pathways implicated in cell survival, apoptosis, protein aggregation, mitochondrial dysfunction, autophagy, oxidative damage and neuroinflammation, contributes to its pathogenesis. MicroRNAs (miRs) are endogenous short non-coding RNA molecules that negatively regulate gene expression at a post-transcriptional level. MiR-124 is one of the most abundantly expressed miRs in the brain that participates in neurogenesis, synapse morphology, neurotransmission, inflammation, autophagy and mitochondrial function. Accumulating pre-clinical evidence shows that miR-124 may act through calpain 1/p25/cyclin-dependent kinases 5 (CDK5), nuclear factor-kappa B (NF-κB), signal transducer and activator of transcription 3 (STAT3), Bcl-2-interacting mediator of cell death (Bim), 5' adenosine monophosphate-activated protein kinase (AMPK) and extracellular signal-regulated kinase (ERK)-mediated pathways to regulate cell survival, apoptosis, autophagy, mitochondrial dysfunction, oxidative damage and neuroinflammation in PD. Moreover, clinical evidence indicates that reduced plasma miR-124 levels may serve as a potential diagnostic biomarker in PD. This review provides an update of the pathogenic implication of miR-124 activity in PD and discusses its targeting potential for the development of future therapeutic strategies.
    Matched MeSH terms: Neuroprotection
  19. Fulltext Human Embryonic Stem Cell-Derived Neural Lineages as In Vitro Models for Screening the Neuroprotective Properties of Lignosus rhinocerus (Cooke) Ryvarden
    Yeo Y, Tan JBL, Lim LW, Tan KO, Heng BC, Lim WL
    Biomed Res Int, 2019;2019:3126376.
    PMID: 33204680 DOI: 10.1155/2019/3126376
    In the biomedical field, there is growing interest in using human stem cell-derived neurons as in vitro models for pharmacological and toxicological screening of bioactive compounds extracted from natural products. Lignosus rhinocerus (Tiger Milk Mushroom) is used by indigenous communities in Malaysia as a traditional medicine to treat various diseases. The sclerotium of L. rhinocerus has been reported to have medicinal properties, including various bioactivities such as neuritogenic, anti-inflammatory, and anticancer effects. This study aims to investigate the neuroprotective activities of L. rhinocerus sclerotial extracts. Human embryonic stem cell (hESC)-derived neural lineages exposed to the synthetic glucocorticoid, dexamethasone (DEX), were used as the in vitro models. Excess glucocorticoids have been shown to adversely affect fetal brain development and impair differentiation of neural progenitor cells. Screening of different L. rhinocerus sclerotial extracts and DEX on the hESC-derived neural lineages was conducted using cell viability and neurite outgrowth assays. The neuroprotective effects of L. rhinocerus sclerotial extracts against DEX were further evaluated using apoptosis assays and Western blot analysis. Hot aqueous and methanol extracts of L. rhinocerus sclerotium promoted neurite outgrowth of hESC-derived neural stem cells (NSCs) with negligible cytotoxicity. Treatment with DEX decreased viability of NSCs by inducing apoptosis. Coincubation of L. rhinocerus methanol extract with DEX attenuated the DEX-induced apoptosis and reduction in phospho-Akt (pAkt) level in NSCs. These results suggest the involvement of Akt signaling in the neuroprotection of L. rhinocerus methanol extract against DEX-induced apoptosis in NSCs. Methanol extract of L. rhinocerus sclerotium exhibited potential neuroprotective activities against DEX-induced toxicity in hESC-derived NSCs. This study thus validates the use of human stem cell-derived neural lineages as potential in vitro models for screening of natural products with neuroprotective properties.
    Matched MeSH terms: Neuroprotection*
  20. Piper sarmentosum Roxb. Root Extracts Confer Neuroprotection by Attenuating Beta Amyloid-Induced Pro-Inflammatory Cytokines Released from Microglial Cells
    Chan EWL, Yeo ETY, Wong KWL, See ML, Wong KY, Gan SY
    Curr Alzheimer Res, 2019;16(3):251-260.
    PMID: 30819080 DOI: 10.2174/1567205016666190228124630
    BACKGROUND: Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder that eventually leads to severe cognitive impairment. Although the exact etiologies of AD still remain elusive, increasing evidence suggests that neuroinflammation cascades mediated by microglial cells are associated with AD. Piper sarmentosum Roxb. (PS) is a medicinal plant reported to possess various biological properties, including anti-inflammatory, anti-psychotic and anti-oxidant activity. However, little is known about the anti-inflammatory activity of PS roots despite their traditional use to treat inflammatory- mediated ailments.

    OBJECTIVE: This study aimed to evaluate the anti-inflammatory and neuroprotective properties of extracts obtained from the roots of PS against beta-amyloid (Aβ)-induced microglial toxicity associated with the production of pro-inflammatory mediators.

    METHOD: BV2 microglial cells were treated with hexane (RHXN), dichloromethane (RDCM), ethyl acetate (REA) and methanol (RMEOH) extracts of the roots of PS prior to activation by Aβ. The production and mRNA expression of pro-inflammatory mediators were evaluated by Griess reagent, ELISA kits and RT-qPCR respectively. The phosphorylation status of p38α MAPK was determined via western blot assay. BV2 conditioned medium was used to treat SH-SY5Y neuroblastoma cells and the neuroprotective effect was assessed using MTT assay.

    RESULTS: PS root extracts, in particular RMEOH significantly attenuated the production and mRNA expression of IL-1β, IL-6 and TNF-α in Aβ-induced BV2 microglial cells. In addition, RHXN, REA and RMEOH extracts significantly reduced nitric oxide (NO) level and the inhibition of NO production was correlated with the total phenolic content of the extracts. Further mechanistic studies suggested that PS root extracts attenuated the production of cytokines by regulating the phosphorylation of p38α MAPK in microglia. Importantly, PS root extracts have protective effects against Aβ-induced indirect neurotoxicity either by inhibiting the production of NO, IL-1β, IL-6, and TNF-α in BV2 cells or by protecting SHSY5Y cells against these inflammatory mediators.

    CONCLUSIONS: These findings provided evidence that PS root extracts confer neuroprotection against Aβ- induced microglial toxicity associated with the production of pro-inflammatory mediators and may be a potential therapeutic agent for inflammation-related neurological conditions including Alzheimer's disease (AD).

    Matched MeSH terms: Neuroprotection/drug effects; Neuroprotection/physiology
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