Therapeutic targets for neurological diseases最新文献_第5页

Stress response modulating effects of lactic acid in mice 乳酸对小鼠应激反应的调节作用

Therapeutic targets for neurological diseases Pub Date : 2014-11-21 DOI: 10.14800/TTND.418

Naveen Shivavedi, S. Chatterjee, Vikas Kumar

{"title":"Stress response modulating effects of lactic acid in mice","authors":"Naveen Shivavedi, S. Chatterjee, Vikas Kumar","doi":"10.14800/TTND.418","DOIUrl":"https://doi.org/10.14800/TTND.418","url":null,"abstract":"Lactic acid is commonly found in sour milk and is often consumed with food, which plays a role in various biochemical processes and used for trauma, surgery, burn injury and as a neuroprotective. Present pilot study was designed to investigate its putative stress response modulating effects in male mice. A battery of behavioural test models viz. stress-induced hyperthermia, tail suspension test and pentobarbital-induced hypnosis was used to assess the adaptogenic activity of lactic acid. Doses of lactic acid (5, 25, 125 and 625 mg/kg) as solution (10 ml/kg) was prepared in distilled water and administered orally for 11 consecutive days. The body weight and body temperature were recorded daily as a measure of stress induced changes. Stress induced hyperthermia test was performed on 1st, 5th, 7th, and 10th day of the treatments. On 11th day, they were subjected to tail suspension test and on day 12th to pentobarbital induce hypnosis test. Stress-induced hyperthermia was reduced by lactic acid in dose dependent manner and also compensated the changed in body weight and basal rectal temperature due to daily handling and intermittent foot-shock stress. Test drug was also reduced the immobility period in tail suspension test and showed considerable effect on onset and duration of sleep in pentobarbital-induce hypnosis test when compared to control, the significant (p<0.05) activity of lactic acid was found at dose 25 mg/kg onwards. These observations indicate that lactic acid has potential for adaptogenic activity, suggesting its use against varied spectrums of psychopathologies associated with stress.","PeriodicalId":90750,"journal":{"name":"Therapeutic targets for neurological diseases","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66658483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 9

Nurr1: A New Insight to Protects Dopaminergic Neurodegeneration in Parkinson’s disease Nurr1:保护帕金森病多巴胺能神经变性的新见解

Therapeutic targets for neurological diseases Pub Date : 2014-11-21 DOI: 10.14800/TTND.436

K. Rekha, R. I. Sivakamasundari

{"title":"Nurr1: A New Insight to Protects Dopaminergic Neurodegeneration in Parkinson’s disease","authors":"K. Rekha, R. I. Sivakamasundari","doi":"10.14800/TTND.436","DOIUrl":"https://doi.org/10.14800/TTND.436","url":null,"abstract":"The developmental transcription factors are important in early neuron specification and differentiation often remains expressed in the adult brain for regulation and maintenances of essential neurophysiological functions. The involvement of transcription factors required for the regulation of long-term survival of central dopaminergic neurons may provide new insight into the etiology and molecular mechanisms leading to dopaminergic cell deaths in Parkinson’s disease (PD). Nurr1, a transcription factor belonging to the orphan nuclear receptor super-family play a vital role in the development, maintenance and survival of dopaminergic neurons. It appears to regulate the expression of dopaminergic markers, and synthesis, transport and storage of dopamine. Decreased Nurr1 expression is found in the autopsied PD midbrains, particularly in neurons containing Lewy bodies, as well as in peripheral lymphocytes of patients with PD. Several variants in Nurr1 gene have been reported in association with PD, in this review we proposed that Nurr1is an essential factor for the maintenance of dopaminergic neuron functions, but it may also play a pivotal role in the pathogenesis of PD.","PeriodicalId":90750,"journal":{"name":"Therapeutic targets for neurological diseases","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66658712","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Promoting oligodendrocyte progenitor cell maturation and remyelination as a novel therapeutical approach for multiple system atrophy 促进少突胶质祖细胞成熟和髓鞘再生作为治疗多系统萎缩的新方法

Therapeutic targets for neurological diseases Pub Date : 2014-11-03 DOI: 10.14800/TTND.409

B. Ettle, J. Schlachetzki, J. Winkler

{"title":"Promoting oligodendrocyte progenitor cell maturation and remyelination as a novel therapeutical approach for multiple system atrophy","authors":"B. Ettle, J. Schlachetzki, J. Winkler","doi":"10.14800/TTND.409","DOIUrl":"https://doi.org/10.14800/TTND.409","url":null,"abstract":"Alpha-synuclein (aSyn) aggregation within mature oligodendrocytes is the characteristic neuropathological feature of multiple system atrophy (MSA). In fact, dysfunction of oligodendrocytes is considered as a primary event in MSA pathogenesis leading to myelin loss and, ultimately, reduced axonal integrity and neuronal cell loss. Oligodendrocyte progenitor cells (OPCs) are widely distributed in the adult central nervous system and represent a potential endogenous source for replacement of such dysfunctional oligodendrocytes. The extent to which OPCs are affected in MSA or even contribute to MSA pathogenesis remains undefined. Thus, we analyzed OPCs post-mortem in MSA brains and in a pre-clinical MSA mouse model expressing aSyn under the myelin basic protein (MBP) promoter. Importantly, we detected elevated numbers of striatal OPCs in MSA and its model 1 . Observing aSyn-positive OPCs in MSA patients, we additionally established two independent in vitro models in order to explore the effect of intracellular aSyn on OPC maturation. Both stable aSyn expressing OPC-like central glia-4 (CG4) cells 1 and transiently aSyn expressing primary OPCs derived from neonatal rats 2 robustly showed a severely reduced maturation. Similarly, primary OPCs exhibit a delayed maturation upon uptake of recombinant aSyn 2 . Taken together, our findings indicate that OPC dysfunction is a pathological feature of MSA. In addition, promoting OPC differentiation may represent a novel and promising interventional strategy for therapeutic approaches in MSA.","PeriodicalId":90750,"journal":{"name":"Therapeutic targets for neurological diseases","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-11-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66658414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Neuroprotective mechanisms of the Rheb/mTORC1 signaling pathway in the adult dopaminergic system in vivo 成人体内多巴胺能系统中Rheb/mTORC1信号通路的神经保护机制

Therapeutic targets for neurological diseases Pub Date : 2014-09-08 DOI: 10.14800/TTND.302

K. H. Jeong, Sang Ryong Kim

{"title":"Neuroprotective mechanisms of the Rheb/mTORC1 signaling pathway in the adult dopaminergic system in vivo","authors":"K. H. Jeong, Sang Ryong Kim","doi":"10.14800/TTND.302","DOIUrl":"https://doi.org/10.14800/TTND.302","url":null,"abstract":"Despite intensive research effort, no effective pharmacological therapies for Parkinson’s disease (PD) have been developed. However, with the development of efficient gene delivery systems, gene therapy for PD has become a focus of research, and increasing evidences suggest that continuous production of neurotrophic factors plays a significant role in the functional restoration of the nigrostriatal dopaminergic (DA) system. We recently reported that viral vector-mediated hRheb(S16H) expression robustly induced glial cell line-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF) expression in adult DA neurons in vivo . Furthermore, we showed that hRheb(S16H)-induced neurotrophic factor expression was dependent on mTORC1 activity and protected nigrostriatal DA projections. Our observations suggest that hRheb(S16H) expression in mature DA neurons facilitates the production of diverse neurotrophic factors such as GDNF and BDNF, and that multiple factors are involved in the maintenance and protection of the nigrostriatal DA system in the adult brain. In this research highlight, we provide a brief overview of our most recent published findings, which demonstrate the neuroprotective mechanisms of hRheb(S16H) on nigrostriatal DA projections in vivo .","PeriodicalId":90750,"journal":{"name":"Therapeutic targets for neurological diseases","volume":"66 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66658355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Transcriptional up-regulation and its impact on poly(Q) disorders 转录上调及其对多(Q)疾病的影响

Therapeutic targets for neurological diseases Pub Date : 2014-09-08 DOI: 10.14800/TTND.312

S. I. Chanu, M. D. Singh, Surajit Sarkar

{"title":"Transcriptional up-regulation and its impact on poly(Q) disorders","authors":"S. I. Chanu, M. D. Singh, Surajit Sarkar","doi":"10.14800/TTND.312","DOIUrl":"https://doi.org/10.14800/TTND.312","url":null,"abstract":"The polyglutamine [poly(Q)] disorders are a class of late-onset genetic disorders those are manifested by progressive loss of neurons in the human brain, leading to cognitive and behavioural impairments. Expansion of CAG trinucleotide repeats in the coding region of the certain genes translate into long poly(Q) tract in the corresponding protein, and consequently, cause gain of function in mutant protein. Underlying the basic cause to neurodegeneration, several mechanisms have been proposed to elucidate the enigma behind the pathology of poly(Q) disorders. However, almost in all instances, till now the exact mechanism(s) of disease pathogenesis remain elusive. In recent years, impairment of cellular transcriptional machinery either due to mutation in the putative poly(Q) genes or sequestration of several nuclear transcription factors has emerged as the main attention for disease pathogenesis. An increased body of evidences suggest that defects in global chromatin structures due to limitation of nuclear transcription factors and chromatin remodelling proteins could be the basic foundation to the poly(Q) pathology. Therefore, balancing the rate of global transcription and compensation of the various survival factors which are otherwise compromised during early stages of disease onset could provide development of some novel therapeutic strategies against these fatal neurodegenerative disorders.","PeriodicalId":90750,"journal":{"name":"Therapeutic targets for neurological diseases","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"66658372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Novel pathological features and potential therapeutic approaches for CADASIL: insights obtained from a mouse model of CADASIL. CADASIL的新病理特征和潜在的治疗方法:从CADASIL小鼠模型获得的见解。

Therapeutic targets for neurological diseases Pub Date : 2014-01-01 Epub Date: 2014-12-02 DOI: 10.14800/ttnd.434

Xiao-Yun Liu, Maria E Gonzalez-Toledo, Austin Fagan, Wei-Ming Duan, Yanying Liu, Siyuan Zhang, Bin Li, Chun-Shu Piao, Lila Nelson, Li-Ru Zhao

{"title":"Novel pathological features and potential therapeutic approaches for CADASIL: insights obtained from a mouse model of CADASIL.","authors":"Xiao-Yun Liu, Maria E Gonzalez-Toledo, Austin Fagan, Wei-Ming Duan, Yanying Liu, Siyuan Zhang, Bin Li, Chun-Shu Piao, Lila Nelson, Li-Ru Zhao","doi":"10.14800/ttnd.434","DOIUrl":"https://doi.org/10.14800/ttnd.434","url":null,"abstract":"Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common condition of hereditary stroke and vascular dementia. CADASIL is caused by Notch3 mutation, leading to progressive degeneration of vascular smooth muscle cells (vSMCs) of the small arteries in the brain. However, the pathogenesis of CADASIL remains largely unknown, and treatment that can stop or delay the progression of CADASIL is not yet available. Using both wild type mice and transgenic mice carrying the human mutant Notch3 gene (CADASIL mice), we have recently characterized the pathological features of CADASIL and determined the therapeutic efficacy of two hematopoietic growth factors, stem cell factor (SCF) and granulocyte colony-stimulating factor (G-CSF) in CADASIL. Our findings have revealed novel pathological changes in the endothelium of cerebral capillaries and in the neural stem cells (NSCs). We have also observed the impairment of cognitive function in CADASIL mice. Moreover, SCF+G-CSF treatment improves cognitive function, inhibits Notch3 mutation-induced vSMC degeneration, cerebral blood bed reduction, cerebral capillary damage, and NSC loss, and increases neurogenesis and angiogenesis. Here we compile an overview of our recently published studies, which provide new insights into understanding the pathogenesis of CADASIL and developing therapeutic strategies for this devastating neurological disease.","PeriodicalId":90750,"journal":{"name":"Therapeutic targets for neurological diseases","volume":"1 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6078431/pdf/nihms-689458.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36379322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2

Astrocyte mediated MMP-9 activation in the synapse dysfunction: An implication in Alzheimer disease. 星形胶质细胞介导的突触功能障碍中的MMP-9激活:与阿尔茨海默病有关。

Therapeutic targets for neurological diseases Pub Date : 2014-01-01 DOI: 10.14800/ttnd.243

Pradip K Kamat, Supriya Swarnkar, Shivika Rai, Vijay Kumar, Neetu Tyagi

{"title":"Astrocyte mediated MMP-9 activation in the synapse dysfunction: An implication in Alzheimer disease.","authors":"Pradip K Kamat, Supriya Swarnkar, Shivika Rai, Vijay Kumar, Neetu Tyagi","doi":"10.14800/ttnd.243","DOIUrl":"https://doi.org/10.14800/ttnd.243","url":null,"abstract":"Alzheimer's disease (AD) is a progressive neurodegenerative disorder that occurs due to spasms of the neurons, resulting in loss of memory and behavioral changes. In particular, synaptic loss has been described as an early event in the pathogenesis of AD. The increasing evidences have suggested the role of many matrix metalloproteinase (MMPs) in central nervous system (CNS) pathology. Many studies showed that MMPs enzymes are important for the pathophysiological process during Alzheimer's disease (AD). It is usually believed that the synaptic dysfunction and synapse loss contribute to the cognitive deficits of patients with AD. Cerebrovascular events such as blood-brain barrier (BBB) disruption lead to neuronal damage as well as neuroinflammation. BBB dysfunctions are observed at an early post injury time point, and are associated with activation of proteases, such as MMPs especially MMP-9 which is actively engage in a neuronal injury in the most of the neurodegenerative disorders. BBB opening is accompanied by astrocytic activation, BBB injury and dysregulation of cerebral blood flow. Activated MMPs disrupt neurovascular unit (NVU) which may starve the neurons and affect the synapse function by altering synaptic plasticity and ultimately lead to cognitive decline. However, how MMPs implicated in synaptic dysfunction what are the mechanism associated with this disparity needs to discuss for better understanding the role of MMP-9 in pathogenesis of AD. In this review, we focused on the role of astrocytes and MMP-9 in synaptic dysfunction. We also, underlined possible pharmacological strategies for drug development that might offer more insight into the pathogenesis of cerebrovascular disease such as stroke and Vascular dementia.","PeriodicalId":90750,"journal":{"name":"Therapeutic targets for neurological diseases","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2014-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4290019/pdf/nihms630721.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32975208","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 36