Neurodegeneration最新文献

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Macrophage and Microglial Cell Response after Common Peroneal Nerve Cut and Crush in C57BL/6J Mice C57BL/6J小鼠腓总神经切断和挤压后巨噬细胞和小胶质细胞的反应
Neurodegeneration Pub Date : 1996-03-01 DOI: 10.1006/neur.1996.0010
He B.P., Tay S.S.W., Leong S.K.
{"title":"Macrophage and Microglial Cell Response after Common Peroneal Nerve Cut and Crush in C57BL/6J Mice","authors":"He B.P.,&nbsp;Tay S.S.W.,&nbsp;Leong S.K.","doi":"10.1006/neur.1996.0010","DOIUrl":"10.1006/neur.1996.0010","url":null,"abstract":"<div><p>The present study, using Mac-1 immunohistochemistry for the detection of macrophages and microglial cells, has investigated the signals for macrophage recruitment in the peripheral nerve fibres and dorsal root ganglia, and microglial cell activation in the dorsal and ventral horns of the spinal cord, at different periods after a right common peroneal (CP) nerve cut or crush in 86 C57BL/6J mice. Though a previous study has demonstrated a delayed regeneration of the peripheral sensory but not the motor fibres in this strain of mice, the present study could not demonstrate a corresponding delay in macrophage recruitment in the L4-L6 dorsal root ganglia and microglial cell activation in the dorsal and ventral horns of the corresponding segments of the spinal cord. In fact, macrophage recruitment and microglial cell activation appeared a short time after the nerve lesion and peaked at 5 days post-operation then subsequently declined. Microglial cells, however, became reactivated at 20–30 days after CP nerve cut, perhaps because of the presence of newly degenerated fibres. In contrast to the above observation, there was no exuberant macrophage recruitment or microglial cell reaction during the period when the majority of the regenerated fibres were detected in the distal segment of the crushed nerve.</p></div>","PeriodicalId":19127,"journal":{"name":"Neurodegeneration","volume":"5 1","pages":"Pages 73-80"},"PeriodicalIF":0.0,"publicationDate":"1996-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/neur.1996.0010","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19704027","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: 6
Blood Superoxide Dismutase, Catalase and Glutathione Peroxidase Activities in Familial and Sporadic Amyotrophic Lateral Sclerosis 家族性和散发性肌萎缩性侧索硬化症的血超氧化物歧化酶、过氧化氢酶和谷胱甘肽过氧化物酶活性
Neurodegeneration Pub Date : 1996-03-01 DOI: 10.1006/neur.1996.0008
Przedborski S. , Donaldson D.M. , Murphy P.L. , Hirsch O. , Lange D. , Naini A.B. , McKenna-Yasek D. , Brown, Jr R.H.
{"title":"Blood Superoxide Dismutase, Catalase and Glutathione Peroxidase Activities in Familial and Sporadic Amyotrophic Lateral Sclerosis","authors":"Przedborski S. ,&nbsp;Donaldson D.M. ,&nbsp;Murphy P.L. ,&nbsp;Hirsch O. ,&nbsp;Lange D. ,&nbsp;Naini A.B. ,&nbsp;McKenna-Yasek D. ,&nbsp;Brown, Jr R.H.","doi":"10.1006/neur.1996.0008","DOIUrl":"10.1006/neur.1996.0008","url":null,"abstract":"<div><p>Recent studies have implicated free radicals in the pathogenesis of amyotrophic lateral sclerosis (ALS), a fatal, paralytic disorder of motor neurons. Herein we report on measurements of erythrocyte activity of the three main free radical scavenging enzymes: copper/zinc superoxide dismutase (Cu/Zn-SOD), catalase, and glutathione peroxidase. We studied 31 patients with sporadic ALS, 18 with familial ALS, and 24 controls, Mean Cu/Zn-SOD activity was reduced in eight familial ALS patients with mutations of Cu/Zn-SOD but was normal in patients with both familial ALS without identified Cu/Zn-SOD mutations and sporadic ALS. Glutathione peroxidase activity was significantly reduced only in sporadic ALS patients treated with insulin-like growth factor I (100 μg/kg). Catalase activity was normal in sporadic and familial ALS. Neither glutathione peroxidase nor catalase activities correlated significantly with duration of symptoms or age at onset. Vitamin E, vitamin C, and β-carotene did not affect any of the three enzyme activities. These observations indicate that disturbances of catalase and glutathione peroxidase function are not likely to be central factors in the pathogenesis of ALS.</p></div>","PeriodicalId":19127,"journal":{"name":"Neurodegeneration","volume":"5 1","pages":"Pages 57-64"},"PeriodicalIF":0.0,"publicationDate":"1996-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/neur.1996.0008","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19704025","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: 57
A Quantitative and Qualitative Analysis of Prion Protein Immunohistochemical Staining in Creutzfeldt-Jakob Disease Using Four Anti Prion Protein Antibodies 四种抗朊蛋白抗体对克雅氏病朊蛋白免疫组化染色的定量和定性分析
Neurodegeneration Pub Date : 1996-03-01 DOI: 10.1006/neur.1996.0012
MacDonald S.T., Sutherland K., Ironside J.W.
{"title":"A Quantitative and Qualitative Analysis of Prion Protein Immunohistochemical Staining in Creutzfeldt-Jakob Disease Using Four Anti Prion Protein Antibodies","authors":"MacDonald S.T.,&nbsp;Sutherland K.,&nbsp;Ironside J.W.","doi":"10.1006/neur.1996.0012","DOIUrl":"10.1006/neur.1996.0012","url":null,"abstract":"<div><p>Creutzfeldt-Jakob disease (CJD) is the most common spongiform encephalopathy affecting humans. Prion protein (PrP) immunohistochemistry may be useful for studying the localization of prion protein and assessing its role in CJD, the accumulation of a specific protease resistant PrP isoform being apparently pathognomic to the spongiform encephalopathies. However, a number of factors influence the results of immunostaining, making interpretation and comparisons between the staining of different PrP antisera difficult. This study has examined qualitatively and quantitatively the staining produced by four antisera raised to a variety of prion protein homologues in two cases of CJD and two age-matched controls. Quantitative analysis was provided through the use of custom designed image analysis software. Kuru, granular and multicentric plaques, cellular, perivacuolar and white matter PrP deposits were observed in CJD cases with all four antisera. No significant immunostaining was seen in the control tissue. Some antibody specific staining patterns were observed qualitatively; however, quantitative analysis showed statistically significant correlations between all the antisera on the diseased brain tissue. Prion protein immunohistochemistry is thus useful in interpreting patterns of protein distribution in diseased brain but care may be required in interpreting the results of a single antibody.</p></div>","PeriodicalId":19127,"journal":{"name":"Neurodegeneration","volume":"5 1","pages":"Pages 87-94"},"PeriodicalIF":0.0,"publicationDate":"1996-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/neur.1996.0012","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19704029","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: 18
The Effect of Oedema and Tissue Swelling on the Measurement of Neuroprotection; a Study using Chlormethiazole and Permanent Middle Cerebral Artery Occlusion in Rats 水肿和组织肿胀对神经保护测量的影响氯甲唑治疗大鼠永久性大脑中动脉闭塞的研究
Neurodegeneration Pub Date : 1996-03-01 DOI: 10.1006/neur.1996.0011
Simon G. Sydserff, Richard A. Green, Alan J. Cross
{"title":"The Effect of Oedema and Tissue Swelling on the Measurement of Neuroprotection; a Study using Chlormethiazole and Permanent Middle Cerebral Artery Occlusion in Rats","authors":"Simon G. Sydserff,&nbsp;Richard A. Green,&nbsp;Alan J. Cross","doi":"10.1006/neur.1996.0011","DOIUrl":"10.1006/neur.1996.0011","url":null,"abstract":"<div><p>The effect of chlormethiazole on hemispheric swelling and cortical tissue water content has been investigated in a model of permanent middle cerebral artery (MCA) occlusion. Chlormethiazole (1 mmol/kg i.p.) or saline was administered 60 min after the induction of ischaemia and the animals sacrificed after 24 hours. The cross sectional area of the left hemisphere was increased by 21.8 + 1.9 % in saline treated rats, but only by 8.4 + 2.4% in chlormethiazole treated rats. However, the reduction in the absolute area of neurodegenerative damage (mm<sup>2</sup>) following chlormethiazole administration was considerably greater than the reduction in hemispheric swelling. Cortical tissue water content of ischaemic brain increased from 76.4% to 84.2% and this was attenuated to 78.8% by chlormethiazole administration. These data demonstrate that, providing damage is measured by fitting tissue slices onto prematched stereotactic maps, the decrease in oedema which accompanies a decrease in neurodegeneration does not result in erroneous estimates of neuroprotection.</p></div>","PeriodicalId":19127,"journal":{"name":"Neurodegeneration","volume":"5 1","pages":"Pages 81-85"},"PeriodicalIF":0.0,"publicationDate":"1996-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/neur.1996.0011","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19704028","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: 22
A Comparison of β-Amyloid Deposition in the Medial Temporal Lobe in Sporadic Alzheimer's Disease, Down's Syndrome and Normal Elderly Brains 散发性阿尔茨海默病、唐氏综合征和正常老年人大脑颞叶内侧β-淀粉样蛋白沉积的比较
Neurodegeneration Pub Date : 1996-03-01 DOI: 10.1006/neur.1996.0005
Armstrong R.A. , Cairns N.J. , Myers D. , Smith C.U.M. , Lantos P.L. , Rossor M.N.
{"title":"A Comparison of β-Amyloid Deposition in the Medial Temporal Lobe in Sporadic Alzheimer's Disease, Down's Syndrome and Normal Elderly Brains","authors":"Armstrong R.A. ,&nbsp;Cairns N.J. ,&nbsp;Myers D. ,&nbsp;Smith C.U.M. ,&nbsp;Lantos P.L. ,&nbsp;Rossor M.N.","doi":"10.1006/neur.1996.0005","DOIUrl":"https://doi.org/10.1006/neur.1996.0005","url":null,"abstract":"The density of beta-amyloid (A beta) deposits was studied in the medial temporal lobe in non-demented individuals and in sporadic Alzheimer's disease (SAD) and Down's syndrome (DS). No A beta deposits were recorded in six of the non-demented cases, while in a further eight cases, these were confined to either the lateral occipitotemporal or parahippocampal gyrus. The mean density of A beta deposits in the cortex was greater in SAD and DS than in non-demented cases but with overlap between patient groups. The mean density of A beta deposits was greater in DS than SAD consistent with a gene dosage effect. The ratio of primitive to diffuse A beta deposits was greater in DS and in non-demented cases than in SAD and the ratio of classic to diffuse deposits was lowest in DS. In all groups, A beta deposits occurred in clusters which were often regularly distributed. In the cortex, the dimension of the A beta clusters was greater in SAD than in the non-demented cases and DS. The data suggest that the development of A beta pathology in the hippocampus could be a factor in the development of DS and SAD. Furthermore, the high density of A beta deposits, and in particular the high proportion of primitive type deposits, may be important in DS while the development of large clusters of A beta deposits may be a factor in SAD.","PeriodicalId":19127,"journal":{"name":"Neurodegeneration","volume":"5 1","pages":"Pages 35-41"},"PeriodicalIF":0.0,"publicationDate":"1996-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/neur.1996.0005","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72252220","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: 22
Microwave Treatment Enhances the Immunostaining of Amyloid Deposits in Both the Transmissible and Non-transmissible Brain Amyloidoses 微波治疗增强了传染性和非传染性脑淀粉样蛋白沉积的免疫染色
Neurodegeneration Pub Date : 1996-03-01 DOI: 10.1006/neur.1996.0013
Pawel P. Liberski , Richard Yanagihara , Paul Brown , Radzislaw Kordek , Iwona Kloszewska , Jolanta Bratosiewicz , Carleton D. Gajdusek
{"title":"Microwave Treatment Enhances the Immunostaining of Amyloid Deposits in Both the Transmissible and Non-transmissible Brain Amyloidoses","authors":"Pawel P. Liberski ,&nbsp;Richard Yanagihara ,&nbsp;Paul Brown ,&nbsp;Radzislaw Kordek ,&nbsp;Iwona Kloszewska ,&nbsp;Jolanta Bratosiewicz ,&nbsp;Carleton D. Gajdusek","doi":"10.1006/neur.1996.0013","DOIUrl":"10.1006/neur.1996.0013","url":null,"abstract":"<div><p>The immunolocalization of amyloid deposits containing either protease-resistant prion protein (PrP) or amyloid β protein (Aβ) in the brains of patients with transmissible or non-transmissible cerebral amyloidoses has been greatly facilitated by the pretreatment of tissue sections with concentrated formic acid. We have investigated whether microwave processing of formalin-fixed tissue sections would obviate the need for formic acid pretreatment. Exposure of brain sections to microwaves, even for periods as brief as 1 sec, greatly enhanced the immunostaining of PrP and Aβ amyloid deposits in both the transmissible and non-transmissible brain amyloidoses. Microwaving for 1 min yielded staining intensities similar to that following pretreatment with concentrated formic acid for 10 min. Moreover, the combination of formic acid pretreatment and microwave processing resulted in an even more intense staining of amyloid deposits. Microwave processing, which is easy to perform and comparatively inexpensive, makes exposure to the potentially toxic fumes of formic acid unnecessary.</p></div>","PeriodicalId":19127,"journal":{"name":"Neurodegeneration","volume":"5 1","pages":"Pages 95-99"},"PeriodicalIF":0.0,"publicationDate":"1996-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/neur.1996.0013","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19704030","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: 15
Apolipoprotein E Genotype and Alzheimer's Disease in an Elderly Norwegian Cohort 载脂蛋白E基因型与老年挪威队列阿尔茨海默病
Neurodegeneration Pub Date : 1996-03-01 DOI: 10.1006/neur.1996.0006
Benjamin R. , Leake A. , McArthur F.K. , Candy J.M. , Ince P.G. , Edwardson J.A. , Torvik A. , Morris C.M. , Bjertness E.
{"title":"Apolipoprotein E Genotype and Alzheimer's Disease in an Elderly Norwegian Cohort","authors":"Benjamin R. ,&nbsp;Leake A. ,&nbsp;McArthur F.K. ,&nbsp;Candy J.M. ,&nbsp;Ince P.G. ,&nbsp;Edwardson J.A. ,&nbsp;Torvik A. ,&nbsp;Morris C.M. ,&nbsp;Bjertness E.","doi":"10.1006/neur.1996.0006","DOIUrl":"10.1006/neur.1996.0006","url":null,"abstract":"<div><p>Apolipoprotein E (Apo E) genotyping was performed on an autopsy cohort of neuropathologically verified non-demented controls and subjects with Alzheimer's disease (AD) resident in nursing homes in the Oslo area. AD was associated with a significantly increased frequency of the Apo E ϵ4 allele; the frequency of the ϵ2 and ϵ3 alleles was lower in AD but not significantly so. Age at death in the control group and the AD group did not differ significantly; neither did age at death nor age at onset of dementia in AD vary according to Apo E genotype, though tendencies towards an earlier age at death was seen in individuals with ϵ4/4 and earlier age at onset dementia in the presence of an ϵ4 allele and a later age of onset the presence of an ϵ3 allele were seen. Possession of an ϵ2 allele had no effect on age at onset of dementia or age at death. Among the possible genotypes there was a trend towards a progression of earliest onset ϵ4/4, ϵ2/4, ϵ3/4, ϵ3/3, ϵ2/3 latest onset of dementia and longest duration ϵ2/4, ϵ4/4, ϵ3/4, ϵ3/3, ϵ2/3 to shortest duration of dementia.</p></div>","PeriodicalId":19127,"journal":{"name":"Neurodegeneration","volume":"5 1","pages":"Pages 43-47"},"PeriodicalIF":0.0,"publicationDate":"1996-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/neur.1996.0006","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19704040","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
Influence of Hydroxypyridones and Desferrioxamine on the Mobilization of Aluminium from Tissues of Aluminium-loaded Rats 羟吡啶酮和去铁胺对载铝大鼠组织中铝动员的影响
Neurodegeneration Pub Date : 1995-12-01 DOI: 10.1006/neur.1995.0054
Anne L. Florence, Annick Gauthier, Roberta J. Ward, Robert R. Crichton
{"title":"Influence of Hydroxypyridones and Desferrioxamine on the Mobilization of Aluminium from Tissues of Aluminium-loaded Rats","authors":"Anne L. Florence,&nbsp;Annick Gauthier,&nbsp;Roberta J. Ward,&nbsp;Robert R. Crichton","doi":"10.1006/neur.1995.0054","DOIUrl":"10.1006/neur.1995.0054","url":null,"abstract":"<div><p>Significantly increased levels of aluminium were assayed in the liver and various brain regions of male Wistar rats after intra-peritoneal injection of aluminium gluconate for a period of 1–2 months. Cessation of aluminium gluconate administration for one month did not alter the tissue content of aluminium, apart from the spleen and hippocampus, indicating temporal stability of the aluminium loading. Administration of desferrioxamine, or one of the hydroxypyridone chelators, decreased tissue aluminium content in the liver and in all regions of the brain investigated. Desferrioxamine was more effective in mobilizing liver aluminium than either of the two hydroxypyridones, CP20 and CP94, whereas the more hydrophobic of the hydroxypyridones, diethyl hydroxypyrid-4-ones, (CP94), was most effective in mobilizing brain aluminium. From the present study it appears that orally active chelators of appropriate hydrophobicity may be extremely effective in mobilizing brain aluminium.</p></div>","PeriodicalId":19127,"journal":{"name":"Neurodegeneration","volume":"4 4","pages":"Pages 449-455"},"PeriodicalIF":0.0,"publicationDate":"1995-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/neur.1995.0054","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19814614","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: 31
Diagnosis and Incidence of Prion (Creutzfeldt-Jakob) Disease: A Retrospective Archival Survey with Implications for Future Research 朊病毒(克雅氏)病的诊断和发病率:对未来研究的回顾性档案调查
Neurodegeneration Pub Date : 1995-12-01 DOI: 10.1006/neur.1995.0043
Bruton C.J. , Bruton R.K. , Gentleman S.M. , Roberts G.W.
{"title":"Diagnosis and Incidence of Prion (Creutzfeldt-Jakob) Disease: A Retrospective Archival Survey with Implications for Future Research","authors":"Bruton C.J. ,&nbsp;Bruton R.K. ,&nbsp;Gentleman S.M. ,&nbsp;Roberts G.W.","doi":"10.1006/neur.1995.0043","DOIUrl":"10.1006/neur.1995.0043","url":null,"abstract":"<div><p>Reliable identification of Creutzfeldt-Jakob disease (CJD) in the UX has become essential following the suggestion that prion disease in cattle (BSE) might transmit, accidentally, to humans who eat contaminated beef. Recent data suggest that some cases of CJD may be clinically unrecognized; in order to examine this proposal we reviewed all cases of dementia (<em>n</em>=1000+) collected in the Runwell Hospital Brain Archive between 1964 and 1990. We identified 19 cases of spongiform encephalopathy of which only 11 were diagnosed before death. These 11 individuals had a characteristic clinical history of CJD (relentless mental deterioration, prominent motor signs and death within a year). Their brains showed little or no external abnormality. In contrast, only two of the eight clinically unrecognized cases had characteristic symptoms. The remaining six presented atypically; their illness lasted 3 years or more, motor signs were much less evident, and simple dementia was the most prominent feature. The brains showed moderate or severe cerebral atrophy. Our data indicate that only about 60% of prion disease cases with pathologically typical spongiform encephalopathy were identified clinically during life. This suggests that human prion disease may be more common than previously supposed and that a further review of the epidemiology of the disease is required</p></div>","PeriodicalId":19127,"journal":{"name":"Neurodegeneration","volume":"4 4","pages":"Pages 357-368"},"PeriodicalIF":0.0,"publicationDate":"1995-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/neur.1995.0043","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19813453","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: 26
The Pharmacotherapy of Alzheimer's Disease Based on the Cholinergic Hypothesis: an Update 基于胆碱能假说的阿尔茨海默病药物治疗:最新进展
Neurodegeneration Pub Date : 1995-12-01 DOI: 10.1006/neur.1995.0042
Marta Weinstock
{"title":"The Pharmacotherapy of Alzheimer's Disease Based on the Cholinergic Hypothesis: an Update","authors":"Marta Weinstock","doi":"10.1006/neur.1995.0042","DOIUrl":"10.1006/neur.1995.0042","url":null,"abstract":"<div><p>Alzheimer's disease (AD) is a neurodegenerative disorder with impairment of cognitive function and personality. The synaptic loss, neuronal atrophy and degeneration of cholinergic nuclei in the basal forebrain may be associated with a reduction in oxidative metabolism of glucose, a fall in acetyl CoA and ATP. Current pharmacological strategies, aimed at increasing cholinergic activity include acetylcholinesterase (AChE) inhibitors, cholinergic agonists, acetylcholine (ACh) releasers and stimulants of nerve growth factors (NGF). AChE inhibitors, physostigmine and Tacrine can slow the decline of cognitive function and memory in some patients with mild or moderate AD, if given for at least 3–6 months in sufficient doses to inhibit brain AChE. Their main disadvantages are low oral bioavailability, peripheral cholinergic hyperactivity and liver toxicity with Tacrine. Newer, less toxic AChE inhibitors, with selective central activity, formulations of physostigmine, selective M<sub>1</sub>and nicotinic agonists are becoming available with improved bioavailability and pharmacokinetics. These may increase the likelihood of therapeutic benefit in AD. Nootropic drugs, e.g. piracetam, which release ACh and are relatively non-toxic could possibly slow the progression of the disease. A combination of an AChE inhibitor, piracetam and a stimulator of NGF may show additive effects on memory processes but with a lower incidence of untoward effects.</p></div>","PeriodicalId":19127,"journal":{"name":"Neurodegeneration","volume":"4 4","pages":"Pages 349-356"},"PeriodicalIF":0.0,"publicationDate":"1995-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1006/neur.1995.0042","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19813452","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: 100
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