Current drug targets. CNS and neurological disorders最新文献_第4页

The putative neuroprotective role of neuropeptide Y in the central nervous system. 神经肽Y在中枢神经系统中可能的神经保护作用。

Current drug targets. CNS and neurological disorders Pub Date : 2005-08-01 DOI: 10.2174/1568007054546153

Ana P Silva, Sara Xapelli, Eric Grouzmann, Cláudia Cavadas

{"title":"The putative neuroprotective role of neuropeptide Y in the central nervous system.","authors":"Ana P Silva, Sara Xapelli, Eric Grouzmann, Cláudia Cavadas","doi":"10.2174/1568007054546153","DOIUrl":"https://doi.org/10.2174/1568007054546153","url":null,"abstract":"Neuropeptide Y (NPY) is one of the most abundant and widely distributed neuropeptides in the mammalian central nervous system (CNS). An overview of the distribution of the G-protein coupled NPY receptor family (Y(1), Y(2), Y(4), Y(5) receptors) in the brain is described. The coexistence of NPY with other neurotransmitters and its wide distribution in several brain areas predict the high importance of NPY as a neuromodulator. Thus, the effect of NPY on the release of several neurotransmitters such as glutamate, gamma-aminobutyric acid (GABA), norepinephrine (NE), dopamine, somastotatin (SOM), serotonin (5-HT), nitric oxide (NO), growth hormone (GH) and corticotropin releasing factor (CRF) is reviewed. A neuroprotective role for NPY under physiological conditions and during hyperactivity such as epileptic-seizures has been suggested. We have shown previously that NPY inhibits glutamate release evoked from hippocampal nerve terminals and has a neuroprotective effect in rat organotypic hippocampal cultures exposed to an excitotoxic insult. Moreover, changes in NPY levels have been observed in different pathological conditions such as brain ischemia and neurodegenerative diseases (Huntington's, Alzheimer's and Parkinson's diseases). Taken together, these studies suggest that NPY and NPY receptors may represent pharmacological targets in different pathophysiological conditions in the CNS.","PeriodicalId":11063,"journal":{"name":"Current drug targets. CNS and neurological disorders","volume":"4 4","pages":"331-47"},"PeriodicalIF":0.0,"publicationDate":"2005-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568007054546153","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25250262","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: 96

Alzheimer's disease-associated neurotoxic mechanisms and neuroprotective strategies. 阿尔茨海默病相关的神经毒性机制和神经保护策略。

Current drug targets. CNS and neurological disorders Pub Date : 2005-08-01 DOI: 10.2174/1568007054546117

C Pereira, P Agostinho, P I Moreira, S M Cardoso, C R Oliveira

{"title":"Alzheimer's disease-associated neurotoxic mechanisms and neuroprotective strategies.","authors":"C Pereira, P Agostinho, P I Moreira, S M Cardoso, C R Oliveira","doi":"10.2174/1568007054546117","DOIUrl":"https://doi.org/10.2174/1568007054546117","url":null,"abstract":"The characteristic hallmarks of Alzheimer's disease (AD), the most common form of dementia in the elderly, include senile plaques, mainly composed of beta-amyloid (Abeta) peptide, neurofibrillary tangles and selective synaptic and neuronal loss in brain regions involved in learning and memory. Genetic studies, together with the demonstration of Abeta neurotoxicity, led to the development of the amyloid cascade hypothesis to explain the AD-associated neurodegenerative process. However, a modified version of this hypothesis has emerged, the Abeta cascade hypothesis, which takes into account the fact that soluble oligomeric forms and protofibrils of Abeta and its intraneuronal accumulation also play a key role in the pathogenesis of the disease. Recent evidence posit that synaptic dysfunction triggered by non fibrillar Abeta species is an early event involved in memory decline in AD. The current understanding of the molecular mechanisms responsible for impaired synaptic function and cognitive deficits is outlined in this review, focusing on oxidative stress and disturbed metal ion homeostasis, Ca(2+) dysregulation, mitochondria and endoplasmic reticulum dysfunction, cholesterol dyshomeostasis and impaired neurotransmission. The activation of apoptotic cell death as a mechanism of neuronal loss in AD, and the prominent role of neuroinflammation in this neurodegenerative disorder, are also reviewed herein. Furthermore, we will focus on the more relevant therapeutical strategies currently used, namely those involving antioxidants, drugs for neurotransmission improvement, hormonal replacement, gamma- and beta- secretase inhibitors, Abeta clearance agents (Abeta immunization, disruption of Abeta fibrils, modulation of the cholesterol-mediated Abeta transport), non-steroidal anti-inflammatory drugs (NSAIDs), microtubules stabilizing drugs and kinase inhibitors.","PeriodicalId":11063,"journal":{"name":"Current drug targets. CNS and neurological disorders","volume":"4 4","pages":"383-403"},"PeriodicalIF":0.0,"publicationDate":"2005-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568007054546117","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25250265","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: 118

Neurodegenerative pathways in Parkinson's disease: therapeutic strategies. 帕金森病的神经退行性通路:治疗策略。

Current drug targets. CNS and neurological disorders Pub Date : 2005-08-01 DOI: 10.2174/1568007054546072

S M Cardoso, P I Moreira, P Agostinho, C Pereira, C R Oliveira

引用次数: 63

Inflammation and neurogenesis in temporal lobe epilepsy. 颞叶癫痫的炎症和神经发生。

Current drug targets. CNS and neurological disorders Pub Date : 2005-08-01 DOI: 10.2174/1568007054546171

L Bernardino, R Ferreira, A J Cristóvao, F Sales, J O Malva

引用次数: 45

Editorial [Hot Topic: Neuron-Glia Interaction (Guest Editor: Joao O. Malva)] 社论[热点话题:神经元-神经胶质相互作用(客座编辑:Joao O. Malva)]

Current drug targets. CNS and neurological disorders Pub Date : 2005-07-31 DOI: 10.2174/1568007054546135

J. Malva

引用次数: 0

The role of COX-1 and COX-2 in Alzheimer's disease pathology and the therapeutic potentials of non-steroidal anti-inflammatory drugs. COX-1和COX-2在阿尔茨海默病病理中的作用及非甾体抗炎药的治疗潜力

Current drug targets. CNS and neurological disorders Pub Date : 2005-06-01 DOI: 10.2174/1568007054038201

Jeroen J M Hoozemans, M Kerry O'Banion

引用次数: 97

The neuroinflammatory response in plaques and amyloid angiopathy in Alzheimer's disease: therapeutic implications. 阿尔茨海默病斑块和淀粉样血管病的神经炎症反应:治疗意义

Current drug targets. CNS and neurological disorders Pub Date : 2005-06-01 DOI: 10.2174/1568007054038229

Annemieke J M Rozemuller, Willem A van Gool, Piet Eikelenboom

{"title":"The neuroinflammatory response in plaques and amyloid angiopathy in Alzheimer's disease: therapeutic implications.","authors":"Annemieke J M Rozemuller, Willem A van Gool, Piet Eikelenboom","doi":"10.2174/1568007054038229","DOIUrl":"https://doi.org/10.2174/1568007054038229","url":null,"abstract":"The amyloid plaques in Alzheimer's disease (AD) brains are co-localised with a broad variety of inflammation-related proteins (complement proteins, acute-phase proteins, pro-inflammatory cytokines) and clusters of activated microglia. The present data suggest that the Abeta depositions in the neuroparenchyma are closely associated with a locally-induced, non-immune-mediated chronic inflammatory response. Clinicopathological and neuroradiological data show that activation of microglia are a relatively early pathogenic event that precedes the process of severe neuropil destruction in patients. Recent gene findings (cDNA microarray) confirm the immunohistochemical findings of an early involvement of inflammatory and regenerative pathways in AD pathogenesis. Abeta deposition, inflammation and regenerative mechanisms are also early pathogenic events in transgenic mice models harbouring the pathological AD mutations, while \"later\" neurodegenerative characteristics are not seen in these models. Next to the plaques, Abeta amyloid deposition is frequently found in the walls of cerebral vessels (cerebral amyloid angiopathy). Most common is the type of amyloid deposition in the walls of meningeal and medium-sized cortical arteries, and more rarely, microcapillary amyloid angiopathy (dyshoric angiopathy). Immunohistochemical studies show that in AD patients, the majority of the amyloid deposits in the walls of the larger vessels is not associated with a chronic inflammatory response in contrast to micro-capillary amyloid angiopathy. In this contribution, we will give an overview of the similarities and differences between the involvement of inflammatory mechanisms in vascular and plaque amyloid in AD and transgenic models. The implications of the reviewed studies for an inflammation-based therapeutical approach in AD will be discussed.","PeriodicalId":11063,"journal":{"name":"Current drug targets. CNS and neurological disorders","volume":"4 3","pages":"223-33"},"PeriodicalIF":0.0,"publicationDate":"2005-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568007054038229","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25153034","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: 96

Preventing activation of receptor for advanced glycation endproducts in Alzheimer's disease. 预防阿尔茨海默病晚期糖基化终产物受体的激活。

Current drug targets. CNS and neurological disorders Pub Date : 2005-06-01 DOI: 10.2174/1568007054038210

L-F Lue, S D Yan, D M Stern, D G Walker

{"title":"Preventing activation of receptor for advanced glycation endproducts in Alzheimer's disease.","authors":"L-F Lue, S D Yan, D M Stern, D G Walker","doi":"10.2174/1568007054038210","DOIUrl":"https://doi.org/10.2174/1568007054038210","url":null,"abstract":"Receptor for advanced glycation endproducts (RAGE), a member of the immunoglobulin superfamily, is a multi-ligand, cell surface receptor expressed by neurons, microglia, astrocytes, cerebral endothelial cells, pericytes, and smooth muscle cells. At least three major types of the RAGE isoforms (full length, C-truncated, and N-truncated) are present in human brains as a result of alternative splicing. Differential expression of each isoform may play a regulatory role in the physiological and pathophysiological functions of RAGE. Analysis of RAGE expression in non-demented and Alzheimer's disease (AD) brains indicated that increases in RAGE protein and percentage of RAGE-expressing microglia paralleled the severity of disease. Ligands for RAGE in AD include amyloid beta peptide (Abeta), S100/calgranulins, advanced glycation endproduct-modified proteins, and amphoterin. Collective evidence from in vitro and in vivo studies supports that RAGE plays multiple roles in the pathogenesis of AD. The major features of RAGE activation in contributing to AD result from its interaction with Abeta, from the positive feedback mechanisms driven by excess amounts of Abeta, and combined with sustained elevated RAGE expression. The adverse consequences of RAGE interaction with Abeta include perturbation of neuronal properties and functions, amplification of glial inflammatory responses, elevation of oxidative stress and amyloidosis, increased Abeta influx at the blood brain barrier and vascular dysfunction, and induction of autoantibodies. In this article, we will review recent advances of RAGE and RAGE activation based on findings from cell cultures, animal models, and human brains. The potential for targeting RAGE mechanisms as therapeutic strategies for AD will be discussed.","PeriodicalId":11063,"journal":{"name":"Current drug targets. CNS and neurological disorders","volume":"4 3","pages":"249-66"},"PeriodicalIF":0.0,"publicationDate":"2005-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568007054038210","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25153037","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: 126

Amyloid associated proteins in Alzheimer's and prion disease. 阿尔茨海默病和朊病毒病中的淀粉样蛋白相关蛋白。

Current drug targets. CNS and neurological disorders Pub Date : 2005-06-01 DOI: 10.2174/1568007054038184

R Veerhuis, R S Boshuizen, A Familian

{"title":"Amyloid associated proteins in Alzheimer's and prion disease.","authors":"R Veerhuis, R S Boshuizen, A Familian","doi":"10.2174/1568007054038184","DOIUrl":"https://doi.org/10.2174/1568007054038184","url":null,"abstract":"Clustering of activated microglia in Abeta deposits is related to accumulation of amyloid associated factors and precedes the neurodegenerative changes in AD. Microglia-derived pro-inflammatory cytokines are suggested to be the driving force in AD pathology. Inflammation-related proteins, including complement factors, acute-phase proteins, pro-inflammatory cytokines, that normally are locally produced at low levels, are increasingly synthesized in Alzheimer's disease (AD) brain. Similar to AD, in prion diseases (Creutzfeldt-Jakob disease, Gerstmann-Sträussler-Scheinker disease and experimentally scrapie infected mouse brain) amyloid associated factors and activated glial cells accumulate in amyloid deposits of conformational changed prion protein (PrPres). Biological properties of Abeta and prion (PrP) peptides, including their potential to activate microglia, relate to Abeta and PrP peptide fibrillogenic abilities that are influenced by certain amyloid associated factors. However, since small oligomers of amyloid forming peptides are more toxic to neurons than large fibrils, certain amyloid associated factors that enhance fibril formation, may sequester the potentially harmful Abeta and PrP peptides from the neuronal microenvironment. In this review the positive and negative actions of amyloid associated factors on amyloid peptide fibril formation and on the fibrillation state related activation of microglia will be discussed. Insight in these mechanisms will enable the design of specific therapies to prevent neurodegenerative diseases in which amyloid accumulation and glial activation are prominent early features.","PeriodicalId":11063,"journal":{"name":"Current drug targets. CNS and neurological disorders","volume":"4 3","pages":"235-48"},"PeriodicalIF":0.0,"publicationDate":"2005-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568007054038184","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25153035","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: 69

The Nrf2-ARE Signalling pathway: promising drug target to combat oxidative stress in neurodegenerative disorders. Nrf2-ARE信号通路:抗神经退行性疾病氧化应激的有希望的药物靶点

Current drug targets. CNS and neurological disorders Pub Date : 2005-06-01 DOI: 10.2174/1568007054038238

Freek L van Muiswinkel, H Bea Kuiperij

{"title":"The Nrf2-ARE Signalling pathway: promising drug target to combat oxidative stress in neurodegenerative disorders.","authors":"Freek L van Muiswinkel, H Bea Kuiperij","doi":"10.2174/1568007054038238","DOIUrl":"https://doi.org/10.2174/1568007054038238","url":null,"abstract":"A large body of evidence indicates that oxidative stress is a salient pathological feature in many neurodegenerative diseases, including Amyotrophic lateral sclerosis, Alzheimer's disease, and Parkinson's disease. In addition to signs of systemic oxidative stress, at the biochemical and neuropathological level, neuronal degeneration in these disorders has been shown to coincide with several markers of oxidative damage to lipids, nucleic acids, and proteins in affected brain regions. Neuroinflammatory processes, often associated with the induction of free radical generating enzymes and the accumulation of reactive astrocytes and microglial cells, are considered as a major source of oxidative stress. Given the pathogenic impact of oxidative stress and neuroinflammation, therapeutic strategies aimed to blunt these processes are considered an effective way to confer neuroprotection. Recently, the nuclear transcription factor Nrf2, that binds to the antioxidant response element (ARE) in gene promoters, has been reported to constitute a key regulatory factor in the co-ordinate induction of a battery of endogenous cytoprotective genes, including those encoding for both antioxidant- and anti-inflammatory proteins. In the present review, besides discussing recent evidence underscoring the thesis that the Nrf2-ARE signalling pathway is an attractive therapeutic target for neurodegenerative diseases, we advocate the view that chemopreventive agents might be suitable candidates to serve as lead compounds for the development of a new class of neuroprotective drugs.","PeriodicalId":11063,"journal":{"name":"Current drug targets. CNS and neurological disorders","volume":"4 3","pages":"267-81"},"PeriodicalIF":0.0,"publicationDate":"2005-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.2174/1568007054038238","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25153038","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: 218