Management Of Neurodegenerative Disorders Research Articles

Ongoing Research on the Role of Gintonin in the Management of Neurodegenerative Disorders.

Neurodegenerative disorders, namely Parkinson’s disease (PD), Huntington’s disease (HD), Alzheimer’s disease (AD), and multiple sclerosis (MS), are increasingly major health concerns due to the increasingly aged population worldwide. These conditions often share the same underlying pathological mechanisms, including elevated oxidative stress, neuroinflammation, and the aggregation of proteins. Several studies have highlighted the potential to diminish the clinical outcomes of these disorders via the administration of herbal compounds, among which gintonin, a derivative of ginseng, has shown promising results. Gintonin is a noncarbohydrate/saponin that has been characterized as a lysophosphatidic acid receptor (LPA Receptor) ligand. Gintonin may cause a significant elevation in calcium levels [Ca2+]i intracellularly, which promotes calcium-mediated cellular effects via the modulation of ion channels and cell surface receptors, regulating the inflammatory effects. Years of research have suggested that gintonin has antioxidant and anti-inflammatory effects against different models of neurodegeneration, and these effects may be employed to tackle the neurological changes. Therefore, we collected the main scientific findings and comprehensively presented them, covering preparation, absorption, and receptor-mediated functions, including effects against Alzheimer’s disease models, Parkinson’s disease models, anxiety and depression-like models, and other neurological disorders, aiming to provide some insights for the possible usage of gintonin in the management of neurodegenerative conditions.

An Evaluation of the Effects of Pyridoxal Phosphate in Chlorpromazineinduced Parkinsonism using Mice.

Parkinsonism is a neurodegenerative disorder with a heavy disease burden, despite the discovery and application of drugs. Current research is beginning to suggest the possible crucial roles of micronutrients such as pyridoxal phosphate in the prevention or management of neurodegenerative disorders. We investigated the possible protective effects of supplemental pyridoxal phosphate in Chlorpromazine (CPZ)-induced Parkinsonism-like changes in mice. Mice were assigned to eight groups of 30 mice each. Groups included Vehicle control (fed standard diet (SD), and administered intraperitoneal {ip} injection of saline and saline per orem), levodopa-carbidopa (LD) group (SD, saline ip and LD per orem), two groups fed pyridoxal phosphate-supplemented diet (at 100 and 200 mg/kg of feed), and administered saline both ip and orally, CPZ group (SD, CPZ ip and saline per orem), CPZ/LD group (SD, CPZ ip and LD per orem) and finally two groups fed pyridoxal phosphate -supplemented diet (at 100 and 200 mg/kg of feed) and administered CPZ ip plus saline per orem. Treatments were administered daily for a period of 21 days to allow for the induction of Parkinsonism features. Body weight and food intake were measured weekly while neurobehavioural and biochemical tests were assessed at the end of the experimental period. Pyridoxal phosphate supplementation was associated with a reduction in CPZ-induced suppression of open-field horizontal locomotion and rearing; and a significant increase in grooming activity. Administration of pyridoxal phosphate-supplemented diet was also associated with improvements in working-memory in CPZ-treated mice; and there was reduction in the index of anxiety and catalepsy score. Pyridoxal phosphate supplementation was associated with significant benefits in CPZ-induced Parkinsonism-like changes in mice.

Neuroprotective effects of antioxidants in the management of neurodegenerative disorders: A literature review.

It is proven that oxidative stress has a pivotal role in the process of neurodegeneration. The use of antioxidants is an attractive method to prevent the incidence of neurodegenerative diseases. We searched major databases (PubMed, Medline, and Google Scholar) using the keywords of neurodegeneration, oxidative stress, and antioxidant for both review and original studies, which have reported the various beneficial effects of antioxidants. About 70 studies were identified for this review. Among various antioxidants, nine antioxidants with the most applications in research investigations were selected and the major findings concerning their protective effects were reviewed. It is concluded that antioxidants can modify and readjust the oxidative stress in the biological milieu, elicit neuroprotective effects, and positively impact the management of neurodegenerative processes.

Diagnosis of Spinocerebellar Ataxia in the West Indies.

BackgroundAccess to medical care in many regions is limited by socioeconomic status, at both the individual and the community level. This report describes the diagnostic process of a family residing on an underserved Caribbean island where routine neurological care is typically addressed by general practitioners, and genetic diagnosis is not available through regular medical channels. The diagnosis and management of neurodegenerative disorders is especially challenging in this setting.Case ReportWe diagnosed a family with spinocerebellar ataxia type 3 (SCA3) in an underdeveloped nation with limited access to genetic medicine and no full-time neurologist.DiscussionMolecular diagnosis of the SCAs can be challenging, even in developed countries. In the Caribbean, genetic testing is generally only available at a small number of academic centers. Diagnosis in this family was ultimately made by utilizing an international, pro bono, research-based collaborative process. Although access to appropriate resources, such as speech, physical, and occupational therapies, is limited on this island because of economic and geographical factors, the provision of a diagnosis appeared to be ultimately beneficial for this family. Identification of affected families highlights the need for access to genetic diagnosis in all communities, and can help direct resources where needed.

Zinc and linoleic acid pre-treatment attenuates biochemical and histological changes in the midbrain of rats with rotenone-induced Parkinsonism

BackgroundStudies have suggested the supplementation of Zinc and Linoleic acid in the management of neurodegenerative disorders but none has investigated the combined effects. Little is known about the neuroprotective effects of either Zinc or Linoleic acid or their combination against development of Parkinsonism. This study was designed to investigate the neuroprotective effects of Zinc and Linoleic acid in rotenone-induced Parkinsonism in rats.MethodsThirty-six young adult female rats weighing 100–150 g divided into six groups were used. Rats were induced with Parkinsonism by subcutaneous administration of rotenone (2.5 mg/kg) once a day for seven consecutive days. The rats received dimethyl sulfoxide (DMSO)/Olive oil or rotenone dissolved in DMSO/Olive oil. Groups III and IV received Zinc (30 mg/kg) or Linoleic acid (150 µl/kg) while group V received a combination of both, 2 weeks prior to rotenone injection. Groups II and VI served as negative (rotenone group) and positive (Levodopa groups) controls respectively. Oxidative stress levels were assessed by estimating Lipid peroxidation (MDA), total antioxidant capacity, Superoxide dismutase, reduced Glutathione (GSH), glutathione peroxidase and catalase in the midbrain. Histological examination was done to assess structural changes in the midbrain.ResultsThere was a significant prevention in lipid peroxidation and decrease in the antioxidant status in intervention-treated groups as compared to the rotenone treated group. In addition, histological examination revealed that Parkinsonian rat brains exhibited neuronal damage. Cell death and reduction in neuron size induced by rotenone was prevented by treatment with zinc, linoleic acid and their combination.ConclusionThese results suggest that zinc and linoleic acid and their combination showed significant neuroprotective activity most likely due to the antioxidant effect.

Anticholinesterase activity and phenolic profile of two medicinal plants (Quassia undulataandSenecio abyssinicus) used in managing cognitive dysfunction in Nigeria

Quassia undulata (QU) and Senecio abyssinicus (SA) leaves are known in folklore in the management of cognitive disorder in Nigeria. However, there is dearth of information about their mechanism of actions. In this study, the effect of QU and SA aqueous extracts on acetylcholinesterase (AChE) and butrylcholinesteras (BChE) activities were determined as well as their antioxidant capacity and phenolic constituents. The result showed that both extracts inhibited AChE and BChE activities and also exhibited antioxidant effect, however, extract from SA had the highest effect compared to that of QU. HPLC analysis revealed the presence of gallic, ellagic, caffeic, quercetin, rutin, and catechin. The inhibition of AChE and BChE activities, and antioxidant capacity of QU and SA could be among the mechanism of actions regarding their use in folklore for the management of cognitive dysfunction. These could therefore be linked to their richness in phenolic compounds, as SA extract exhibited higher effects. Practical applications Many plants have been used traditionally in the treatment of various disorders owing to their bioactivity. The outcome of this research provides biochemical information to the folkloric use of Quassia undulate and Senecio abyssinicus in the management of neurodegenerative disorder, and also to the pharmacologist with an option to synthesize drugs with little or no side effects.

CEREBROPROTECTIVE EFFECTS OF GANGETIN ALKALOIDS ON SODIUM NITRITE-INDUCED HYPOXIA AND ETHANOL-INDUCED NEURODEGENERATION

Cognitive impairment is a multidimensional and complicated concept that subsumes the attention, concentration, learning, memory, problem-solving ability, visuospatial abilities, mental flexibility, psychomotor efficiency and manual dexterity. Objective: To study the effects of Gangetin alkaloids from the seeds of Desmodium gangeticum on cognitive deficit mice. Gangetin alkaloids were screened for Sodium nitrite induced hypoxia and Ethanol induced neurodegeneration using behavioral models such as rotarod, Passive shock avoidance paradigm, special water bottle case model, elevated plus maze and Morris water maze. GA (5, 2.5 and 1.25 mg/kg p.o.) were administered to the mice. Acquisition, retention, Transfer latency (TLT), Time spent in target quadrant (TSTQ), Step down latency (SDL) and Escape latency (ELT) and biochemical parameters such as AChE, MAOA, TBARS, epinephrine, 5 HT were determined. DNA fragmentation studies were conducted which were compared with donepezil. GA (5, 2.5 and 1.25 mg kg(-1) p.o.) significantly (p < 0.001) protected the Sodium nitrite induced memory impairment by decreasing the time require to find the water bottle in special water bottle case model. GA improved acquisition and retention memory significantly (p < 0.001) by decreasing the Transfer Latency Time (TLT), escape latency time, TSTQ and increased the Step Down Latency (SDL. GA inhibited Acetylcholinestrase (p < 0.01) activity, increased GSH,decreased TBARS and inhibited MAOA activity. Reduced the metabolism of epinephrine, 5-HT. GA (5 mg kg(-1)) protected the DNA fragmentation of frontotemporal cortex from hypoxic effects. Gangetin alkaloids are beneficial in the management of neurodegenerative disorders particularly for Alzheimer’s disease.

Evaluation of the effect of natural peptide 'Urocortin' on corticotrophin releasing factor (CRF) receptor expression in ND7/23 cells

CRF receptors are involved in the stress management of the cells and are believed to have a cytoprotective role in the body. CRF receptors have been reported to be potential drug targets for the treatment of neurodegenerative disorders. The cell line used in the study is ND7/23 (mouse neuroblastoma and rat dorsal root ganglion neuron hybridoma). The aim of the study was to confirm the expression of CRF receptors in ND7/23 cells and to determine if urocortin (Ucn) can enhance the expression of CRF receptors. ND7/23 cells were cultured in RPMI 1640 media and cells grown after the second passage were used for the experiments. RNA was extracted from the cells and amplified by RT-PCR to confirm the presence of CRF receptors. The cells were then subjected to oxidative stress by hydrogen peroxide (0.00375%) and divided into two groups i.e. control and Ucn (10-8 μM) treated. Later RNA was extracted from both group of cells and PCR was performed. Finally, densitometry analysis was conducted on the agarose gel to determine the quantity of PCR product formed. PCR experiment confirmed the expression of both CRF-R1 and CRF-R2 in the cell line, but CRF-R1 was found to be expressed more strongly. Densitometry analysis of the PCR product and calculation of the relative expression of CRF receptors indicated a higher level of expression of CRF receptors in samples treated with Ucn as compared to those that were kept untreated. The results indicate that Ucn may be useful for the management of neuro-degenerative disorders and further studies may be carried out to establish its use as a therapeutic agent.

Medicinal plants in management of type 2 diabetes and neurodegenerative disorders.

Medicinal plants in management of type 2 diabetes and neurodegenerative disorders.

Recent updates in the treatment of neurodegenerative disorders using natural compounds.

Neurodegenerative diseases are characterized by protein aggregates and inflammation as well as oxidative stress in the central nervous system (CNS). Multiple biological processes are linked to neurodegenerative diseases such as depletion or insufficient synthesis of neurotransmitters, oxidative stress, abnormal ubiquitination. Furthermore, damaging of blood brain barrier (BBB) in the CNS also leads to various CNS-related diseases. Even though synthetic drugs are used for the management of Alzheimer's disease, Parkinson's disease, autism, and many other chronic illnesses, they are not without side effects. The attentions of researchers have been inclined towards the phytochemicals, many of which have minimal side effects. Phytochemicals are promising therapeutic agents because many phytochemicals have anti-inflammatory, antioxidative as well as anticholinesterase activities. Various drugs of either synthetic or natural origin applied in the treatment of brain disorders need to cross the BBB before they can be used. This paper covers various researches related to phytochemicals used in the management of neurodegenerative disorders.

Acetylcholinesterase Inhibitors from Croton sylvaticus Ethyl Acetate Leaf Extract and their Mutagenic Effects

Croton sylvaticus is a medicinal plant widely employed in the management of inflammatory conditions, infections and oxidative stress related diseases such as insomnia, abdominal and internal inflammations. The activities demonstrated by the plant extracts support that its constituents possess the ability to reduce oxidative damage to body cells. Repeated column fractionation of the ethyl acetate fraction of a 20% aqueous methanol leaf extract using acetylcholinesterase (AChE) activity directed on Sephadex LH-20 afforded three compounds identified by mass spectrometry, and 1D and 2D NMR spectroscopy as: 2′-(3″,4″-dihydroxyphenyl)-ethyl-4-hydroxybenzoate (1), 3, 3′, 4′, 5, 7-pentahydroxyflavone (quercetin) (2), and 3, 4′, 5, 7-tetrahydroxyflavone (kaempferol) (3). These compounds are reported from the leaf extracts of C. sylvaticus for the first time and compound 1 is a new natural product. The microplate technique was used to determine the inhibitory effects of the plant extracts (crude and solvent fractions) and isolated compounds against AChE. The IC50 values of the compounds ranged from 60.7 to 415.0 μg/mL, with compound 2 having the best inhibitory activity; the IC50 values of the plant crude extract and solvent fractions ranged from 235.0 to 4695.0 μg/mL. The ethyl acetate fraction had the best inhibitory activity (IC50=235.0 μg/mL). The three compounds showed no mutagenic effects against Salmonella typhimurium tester strains TA98 and TA100. The activity demonstrated by these compounds suggests that they could be effective in the management of neurodegenerative disorders.

Acetylcholinesterase inhibitory activity and mutagenic effects of Croton penduliflorus leaf extract constituents

Croton penduliflorus is a medicinal plant widely employed in the management of inflammatory conditions, infections and oxidative stress related diseases. The activities demonstrated by leaf extracts indicate that they possess the ability to reduce oxidative damage to cells. Repeated column fractionation of the ethyl acetate fraction of a 20% aqueous methanol leaf extract of C. penduliflorus on Sephadex LH-20 afforded four phenolic compounds: quercetin-3-O-rhamnoside (1), kaempferol-3-O-rhamnoside (2), protocatechualdehyde (3A) and its solvent derived dimer (3B) along with p-hydroxybenzoic acid (4). Compound 3B is described for the first time and its significance in bioassay is briefly outlined. Structure elucidation of the isolated compounds was carried out using spectroscopic techniques. The inhibitory properties of the four compounds against acetylcholinesterase were determined using the microplate assay. The IC50 values of the isolated compounds ranged from 87.9 to 1231.9μM, with compound 2 having the best inhibitory activity (IC50=87.9μM). The four isolated compounds showed no mutagenic effects against Salmonella typhimurium tester strains TA98 and TA100. The moderate activity demonstrated by these compounds suggests that they could be helpful in the management of neurodegenerative disorders.

Psychopharmacological investigations on the benefits of Ageratum conyzoides in the modulation of neurodegenerative disorder of Alzheimer’s type

Alzheimer’s disease is a neurodegenerative disease of the central nervous system that leads to dementia, behavioural and cognitive impairments. The study was aimed to investigate the effect of Ageratum conyzoides (AC) on memory and whole brain acetylcholinesterase activity in mice by employing the exteroceptive behavioural models like elevated plus maze and Morris water maze and interoceptive behavioural models like scopolamine and natural ageing inducing amnesia. AC (250, 500 and 750 mg/kg, orally p.o.) produced a dose-dependent improvement in learning capability and retention memory of both young and aged mice. Furthermore, it also reversed the scopolamine (0.4 mg/kg, i.p.) and natural ageing-induced amnesia in young and old mice respectively. One more important thing about AC is that it increases the acetylcholine indirectly by reducing the whole brain acetylcholinestrease activity. Hence AC may have a beneficial effect in the management of neurodegenerative disorder of Alzheimer’s type. Key words: Acetylcholinestrease, aged mice, ageratum conyzoides, scopolamine

High‐field magnetic resonance imaging of brain iron: birth of a biomarker?

The brain has an unusually high concentration of iron, which is distributed in an unusual pattern unlike that in any other organ. The physiological role of this iron and the reasons for this pattern of distribution are not yet understood. There is increasing evidence that several neurodegenerative diseases are associated with altered brain iron metabolism. Understanding these dysmetabolic conditions may provide important information for their diagnosis and treatment. For many years the iron distribution in the human brain could be studied effectively only under postmortem conditions. This situation was changed dramatically by the finding that T2-weighted MR imaging at high field strength (initially 1.5 T) appears to demonstrate the pattern of iron distribution in normal brains and that this imaging technique can detect changes in brain iron concentrations associated with disease states. Up to the present time this imaging capability has been utilized in many research applications but it has not yet been widely applied in the routine diagnosis and management of neurodegenerative disorders. However, recent advances in the basic science of brain iron metabolism, the clinical understanding of neurodegenerative diseases and in MRI technology, particularly in the availability of clinical scanners operating at the higher field strength of 3 T, suggest that iron-dependent MR imaging may soon provide biomarkers capable of characterizing the presence and progression of important neurological disorders. Such biomarkers may be of crucial assistance in the development and utilization of effective new therapies for Alzheimer's and Parkinson's diseases, multiple sclerosis and other iron-related CNS disorders which are difficult to diagnose and treat.

New strategies for the treatment of Parkinson's disease hold considerable promise for the future management of neurodegenerative disorders.

Neurodegenerative diseases are often considered incurable with no efficient therapies to modify or halt the progress of disease, and ultimately lead to reduced quality of life and to death. Our knowledge of the nervous system in health and disease has, however, increased considerably during the last fifty years and today, neuroscience reveals promising new strategies to deal with disorders of the nervous system. Some of these results have been implemented with success in the treatment of Parkinson's disease, a common neurodegenerative illness affecting approximately 1% of the population aged seventy or more. Parkinson's disease is characterized by a massive loss of dopaminergic neurons in the substantia nigra, leading to severe functional disturbance of the neuronal circuitry in the basal ganglia. A thorough description of basal ganglia circuitry in health and disease is presented. We describe how the functional disturbances seen in Parkinson's disease may be corrected at specific sites in this circuitry by medical treatment or, in advanced stages of Parkinson's disease, by neurosurgical methods. The latter include lesional surgery, neural transplantation and deep brain stimulation, together with future treatment strategies using direct or indirect implantation of genetically modified cell-lines capable of secreting neurotrophic factors or neurotransmitters. Advantages and disadvantages are briefly mentioned for each strategy and the implications for the future and the possible use of these interventions in other neurodegenerative diseases are discussed, with special emphasis on deep brain stimulation.

The recognition, diagnosis and management of neurodegenerative disorders

Both general and community paediatricians play an important role in recognizing neurodegenerative disorders. However, many will consider that the diagnosis and management of such disorders falls largely outside their expertise, and will, quite rightly, refer such children quickly to a paediatric neurologist. They will still, however, continue to have a very important role to play. Many different neurological conditions lead to either developmental arrest (which may be followed by loss of skills) or regression. Such a pattern is not only due to rare enzyme defects and this pattern of disability may not even have an organic basis. General paediatricians will play an important role in helping to reach the correct diagnosis. Once a diagnosis has been made then the children should be cared for on a shared care basis, with the local paediatrician again being pivotal in liaising with local services and providing support for the child and his or her family. This article describes how to recognize a neurodegenerative disorder, important features which help to make a diagnosis and management options. It is not possible to mention every single disorder in this brief article, but the same broad principles apply.