Pub Date : 2017-04-19DOI: 10.4172/2161-0460.1000320
Liuzhu Yang, Ruizhen Li, Bo Wu, Jinau Luo, Zhong Chen, Xin-Ping, Yan, Wei Tan
Spinal Cord Injury (SCI) is a complex process which leads to destruction of neuronal tissue and also vascular structure. Recent many studies have shown erythropoietin (EPO) has neuro-protective effects in acute SCI animal models. Alzheimer’s disease (AD), Parkinson’s disease (PD) and SCI belong to central nervous system diseases, a few studies also indicated that EPO may be effective for AD and PD. In this a short review article, we provide a short overview of the animal and human studies on rhEPO in SCI, AD and PD. Further clinical studies should reveal whether derivatives and variants of EPO provide any benefits over the clinical application EPO to against SCI, AD and PD in the experimental studies.
{"title":"Point of View about Erythropoietin in Treatment of Central NervousSystem Diseases","authors":"Liuzhu Yang, Ruizhen Li, Bo Wu, Jinau Luo, Zhong Chen, Xin-Ping, Yan, Wei Tan","doi":"10.4172/2161-0460.1000320","DOIUrl":"https://doi.org/10.4172/2161-0460.1000320","url":null,"abstract":"Spinal Cord Injury (SCI) is a complex process which leads to destruction of neuronal tissue and also vascular structure. Recent many studies have shown erythropoietin (EPO) has neuro-protective effects in acute SCI animal models. Alzheimer’s disease (AD), Parkinson’s disease (PD) and SCI belong to central nervous system diseases, a few studies also indicated that EPO may be effective for AD and PD. In this a short review article, we provide a short overview of the animal and human studies on rhEPO in SCI, AD and PD. Further clinical studies should reveal whether derivatives and variants of EPO provide any benefits over the clinical application EPO to against SCI, AD and PD in the experimental studies.","PeriodicalId":15012,"journal":{"name":"Journal of Alzheimers Disease & Parkinsonism","volume":"390 1","pages":"1-4"},"PeriodicalIF":0.0,"publicationDate":"2017-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85403535","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}
Pub Date : 2017-04-17DOI: 10.4172/2161-0460.1000319
Z. Zheng, W. Poon
Parkinson’s disease (PD) is one of the most common neurodegenerative diseases affecting the aging population worldwide. Levodopa (L-DOPA) is the gold standard of PD therapy, which is administrated for symptomatic treatment. However, long-term application of L-DOPA leads to less effectiveness and a dose-dependent side effect of dyskinesia. Therefore, to help understand the pathogenesis and clarify potential therapeutic strategies, a great effort is made for the preclinical research on experimental PD models. Since the variety of the animal models is employed in the research work of PD, a controversy has arisen over the reproducibility of experimental models to clinical Parkinsonism. The experimental paradigms are diverse, with which partial Parkinsonism features can be induced in rodents, while others may be limited. Rodent models need to be validated for further use in pathophysiological and therapeutic investigations. This review summarizes the characteristics of the commonly used experimental PD models on rodents, including both unilateral and bilateral models, which may provide useful ideas on selection the most applicable animal model on specific aims of PD research. In conclusion, bilateral models are more consistent with the natural pathogenic process of PD, although there currently exists no model completely reproducing the clinical characteristics of human patients.
{"title":"Rodent Model of ParkinsonâÂÂs Disease: Unilateral or Bilateral?","authors":"Z. Zheng, W. Poon","doi":"10.4172/2161-0460.1000319","DOIUrl":"https://doi.org/10.4172/2161-0460.1000319","url":null,"abstract":"Parkinson’s disease (PD) is one of the most common neurodegenerative diseases affecting the aging population worldwide. Levodopa (L-DOPA) is the gold standard of PD therapy, which is administrated for symptomatic treatment. However, long-term application of L-DOPA leads to less effectiveness and a dose-dependent side effect of dyskinesia. Therefore, to help understand the pathogenesis and clarify potential therapeutic strategies, a great effort is made for the preclinical research on experimental PD models. Since the variety of the animal models is employed in the research work of PD, a controversy has arisen over the reproducibility of experimental models to clinical Parkinsonism. The experimental paradigms are diverse, with which partial Parkinsonism features can be induced in rodents, while others may be limited. Rodent models need to be validated for further use in pathophysiological and therapeutic investigations. This review summarizes the characteristics of the commonly used experimental PD models on rodents, including both unilateral and bilateral models, which may provide useful ideas on selection the most applicable animal model on specific aims of PD research. In conclusion, bilateral models are more consistent with the natural pathogenic process of PD, although there currently exists no model completely reproducing the clinical characteristics of human patients.","PeriodicalId":15012,"journal":{"name":"Journal of Alzheimers Disease & Parkinsonism","volume":"23 1","pages":"1-5"},"PeriodicalIF":0.0,"publicationDate":"2017-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73891862","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}
Pub Date : 2017-04-10DOI: 10.4172/2161-0460.1000318
Myeongjoo Son Seyeon Oh, SoJung Lee, K. Byun
Receptor for advanced glycation end products (RAGE) and its ligands have been reported to be involved in the progressions of neurodegenerative diseases, including Alzheimer’s and Parkinson’s disease. Recently microglia activated by immunological stimuli, cytokines, or oxidative stress were reported to synthesize and secrete RAGE ligands including AGEs, HMGB1, and S100 in neurodegenerative diseases. Furthermore, RAGE/ligand binding has been implicated in neuroinflammation and in the progression of neurodegenerative diseases through a RAGEmediated pathway in neurons. A number of RAGE inhibitors, such as, antagonists, small RAGE inhibitors, anti-RAGE antibody, and soluble RAGE, have been shown to interfere with RAGE/ligand binding and to reduce RAGE ligand accumulation, microglia activation, and neuronal cell death in neurodegenerative diseases. Accordingly, RAGE inhibitors present an attractive therapeutic target in neurodegenerative diseases, and RAGE ligands might be useful diagnostic targets. Some human studies have shown RAGE ligand distributions in brain, serum, and cerebrospinal fluid are promising biomarkers for early disease detection and that these ligands might play important roles during early disease stages. Taken together, RAGE ligands and RAGE inhibitors appear to be good therapeutic and diagnostic candidates for neurodegenerative diseases.
{"title":"Ligands of Receptor for Advanced Glycation End-Products Produced byActivated Microglia are Critical in Neurodegenerative Diseases","authors":"Myeongjoo Son Seyeon Oh, SoJung Lee, K. Byun","doi":"10.4172/2161-0460.1000318","DOIUrl":"https://doi.org/10.4172/2161-0460.1000318","url":null,"abstract":"Receptor for advanced glycation end products (RAGE) and its ligands have been reported to be involved in the progressions of neurodegenerative diseases, including Alzheimer’s and Parkinson’s disease. Recently microglia activated by immunological stimuli, cytokines, or oxidative stress were reported to synthesize and secrete RAGE ligands including AGEs, HMGB1, and S100 in neurodegenerative diseases. Furthermore, RAGE/ligand binding has been implicated in neuroinflammation and in the progression of neurodegenerative diseases through a RAGEmediated pathway in neurons. A number of RAGE inhibitors, such as, antagonists, small RAGE inhibitors, anti-RAGE antibody, and soluble RAGE, have been shown to interfere with RAGE/ligand binding and to reduce RAGE ligand accumulation, microglia activation, and neuronal cell death in neurodegenerative diseases. Accordingly, RAGE inhibitors present an attractive therapeutic target in neurodegenerative diseases, and RAGE ligands might be useful diagnostic targets. Some human studies have shown RAGE ligand distributions in brain, serum, and cerebrospinal fluid are promising biomarkers for early disease detection and that these ligands might play important roles during early disease stages. Taken together, RAGE ligands and RAGE inhibitors appear to be good therapeutic and diagnostic candidates for neurodegenerative diseases.","PeriodicalId":15012,"journal":{"name":"Journal of Alzheimers Disease & Parkinsonism","volume":"25 1","pages":"1-5"},"PeriodicalIF":0.0,"publicationDate":"2017-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79322036","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}
Pub Date : 2017-04-04DOI: 10.4172/2161-0460.1000317
Franziska Scheiwein, K. Ishii, C. Hosokawa, H. Kaida, T. Hyodo, Kohei Hanaoka, M. Brendel, P. Bartenstein, A. Rominger, T. Murakami
Purpose: In subjects showing an increased level of 11C-Pittsburgh compound B (PiB) in positron emission tomography (PET) imaging of the brain, two groups can be distinguished: those with and without elevated PiB uptake in the striatum. We examined regional PiB uptake differences between these groups, and additionally compared them with PiB-negative subjects. Methods: This study included 141 subjects complaining of cognitive impairment. Their clinical diagnoses were Alzheimer’s disease (AD), mild cognitive impairment, dementia with Lewy bodies, frontotemporal lobar degeneration, or subjective cognitive impairment. PiB and 18F-fluorodeoxy-D-glucose (FDG) PET were performed in all subjects. PiB PET images were visually classified into three groups: 1) PiB-positive with uptake in any region of the cortex accompanied by striatal PiB uptake (STRPOS), 2) PiB-positive with cortical uptake but without striatal PiB uptake (STRNEG), and 3) both cortex and striatum PiB-negative (PiBNEG). Standardised uptake value ratios (SUVR) and regional differences in PiB uptake were evaluated using voxelbased analysis of PiB and FDG uptake images. Results: Eighty subjects were visually rated as PiB-positive: 11 had no increased PiB uptake in the striatal area, while 69 showed an elevated striatal PiB level. Sixty-one subjects were PiB-negative. Mean cortical SUVR was 1.46 ± 0.23 for STRNEG, 2.00 ± 0.44 for STRPOS and 0.99 ± 0.19 for PiBNEG. Apart from the striatum, PiB accumulation in the medial orbitofrontal cortex of STRPOS subjects was higher than in STRNEG subjects. No significant differences in regional FDG distribution were observed. Conclusion: PiB-positive cases with high striatal PiB uptake have an increased mean cortical SUVR in comparison to PiB-positive subjects without striatal uptake. This difference is most distinctive in the orbitofrontal cortex. We conclude that a high amyloid load in the striatum is linked to amyloid deposition occurring mostly in the frontal region, and may occur later in the course of AD progression.
{"title":"Regional Differences in Amyloid Deposition between 11C-Pib PET PositivePatients with and without Elevated Striatal Amyloid Uptake","authors":"Franziska Scheiwein, K. Ishii, C. Hosokawa, H. Kaida, T. Hyodo, Kohei Hanaoka, M. Brendel, P. Bartenstein, A. Rominger, T. Murakami","doi":"10.4172/2161-0460.1000317","DOIUrl":"https://doi.org/10.4172/2161-0460.1000317","url":null,"abstract":"Purpose: In subjects showing an increased level of 11C-Pittsburgh compound B (PiB) in positron emission tomography (PET) imaging of the brain, two groups can be distinguished: those with and without elevated PiB uptake in the striatum. We examined regional PiB uptake differences between these groups, and additionally compared them with PiB-negative subjects. Methods: This study included 141 subjects complaining of cognitive impairment. Their clinical diagnoses were Alzheimer’s disease (AD), mild cognitive impairment, dementia with Lewy bodies, frontotemporal lobar degeneration, or subjective cognitive impairment. PiB and 18F-fluorodeoxy-D-glucose (FDG) PET were performed in all subjects. PiB PET images were visually classified into three groups: 1) PiB-positive with uptake in any region of the cortex accompanied by striatal PiB uptake (STRPOS), 2) PiB-positive with cortical uptake but without striatal PiB uptake (STRNEG), and 3) both cortex and striatum PiB-negative (PiBNEG). Standardised uptake value ratios (SUVR) and regional differences in PiB uptake were evaluated using voxelbased analysis of PiB and FDG uptake images. Results: Eighty subjects were visually rated as PiB-positive: 11 had no increased PiB uptake in the striatal area, while 69 showed an elevated striatal PiB level. Sixty-one subjects were PiB-negative. Mean cortical SUVR was 1.46 ± 0.23 for STRNEG, 2.00 ± 0.44 for STRPOS and 0.99 ± 0.19 for PiBNEG. Apart from the striatum, PiB accumulation in the medial orbitofrontal cortex of STRPOS subjects was higher than in STRNEG subjects. No significant differences in regional FDG distribution were observed. Conclusion: PiB-positive cases with high striatal PiB uptake have an increased mean cortical SUVR in comparison to PiB-positive subjects without striatal uptake. This difference is most distinctive in the orbitofrontal cortex. We conclude that a high amyloid load in the striatum is linked to amyloid deposition occurring mostly in the frontal region, and may occur later in the course of AD progression.","PeriodicalId":15012,"journal":{"name":"Journal of Alzheimers Disease & Parkinsonism","volume":"18 1","pages":"1-7"},"PeriodicalIF":0.0,"publicationDate":"2017-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90238001","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}
Pub Date : 2017-03-31DOI: 10.4172/2161-0460.1000316
M. Shimono, A. Senju
The classification of neuronal ceroid lipofuscinoses (NCLs) had been clinically divided according to the age at the onset of symptoms: infantile, late infantile, juvenile and adult NCLs. However, this classification cannot always predict the causative gene; i.e., CLN1, for example, causes not only infantile NCL but also late onset infantile and adult NCLs. In 2012, a new classification for the NCLs that takes into account recent genetic and biochemical advances. This short review commentary focuses on the NCLs which might cause symptoms in children from neonate to preschooler age: CLN10 (neonatal), CLN1 (6-48 months), CLN14 (8-24 months), CLN2 (1-6 years), CLN3 (4-7 years), CLN5 (4-6 years), CLN6 (18 months-8 years), CLN7 (2-7 years) and CLN8 (5-10 years). There is no fundamental therapy, but there is the trial of some cures.
{"title":"A Short Commentary of Neuronal Ceroid Lipofuscinoses; Phenotypes inCongenital to Preschooler","authors":"M. Shimono, A. Senju","doi":"10.4172/2161-0460.1000316","DOIUrl":"https://doi.org/10.4172/2161-0460.1000316","url":null,"abstract":"The classification of neuronal ceroid lipofuscinoses (NCLs) had been clinically divided according to the age at the onset of symptoms: infantile, late infantile, juvenile and adult NCLs. However, this classification cannot always predict the causative gene; i.e., CLN1, for example, causes not only infantile NCL but also late onset infantile and adult NCLs. In 2012, a new classification for the NCLs that takes into account recent genetic and biochemical advances. This short review commentary focuses on the NCLs which might cause symptoms in children from neonate to preschooler age: CLN10 (neonatal), CLN1 (6-48 months), CLN14 (8-24 months), CLN2 (1-6 years), CLN3 (4-7 years), CLN5 (4-6 years), CLN6 (18 months-8 years), CLN7 (2-7 years) and CLN8 (5-10 years). There is no fundamental therapy, but there is the trial of some cures.","PeriodicalId":15012,"journal":{"name":"Journal of Alzheimers Disease & Parkinsonism","volume":"78 1","pages":"1-3"},"PeriodicalIF":0.0,"publicationDate":"2017-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79691390","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}
Pub Date : 2017-03-29DOI: 10.4172/2161-0460.1000315
E. Tarnow
Objective: Recently it was shown that free recall consists of two stages: the first few recalls empty working memory and a second stage, a reactivation stage, concludes the recall. It was also shown that the serial position curve changes in mild Alzheimer’s disease – lowered total recall and lessened primacy - are similar to second stage recall and different from recall from working memory. Here we wanted to investigate whether there were any free recall first stage changes in more advanced Alzheimer’s disease. Methods: The Tarnow Unchunkable Test (TUT) uses double integer items to separate out only the first stage, the emptying of working memory, by making it difficult to reactivate items due to the lack of intra-item relationships. Results: TUT is found to be gender and culture independent with small dependencies on age and years of education. TUT 3-item test selects out diagnosed Alzheimer’s disease but not amnestic MCI or non-amnestic MCI. On average, diagnosed Alzheimer’s disease is correlated with a loss of 0.6 memory pointers (out of an average of 2.6 pointers) and this is most pronounced for the later serial positions. Conclusion: Diagnosed Alzheimer’s disease is correlated with a loss of 0.6 working memory pointers. The identification of a lost memory pointer may have implications for improved stage definitions of Alzheimer’s disease and for remediation therapy via working memory capacity management.
{"title":"Preliminary Evidence: Diagnosed AlzheimerâÂÂs Disease but not MCI AffectsWorking Memory: 0.6 of 2.6 Memory Pointers Lost","authors":"E. Tarnow","doi":"10.4172/2161-0460.1000315","DOIUrl":"https://doi.org/10.4172/2161-0460.1000315","url":null,"abstract":"Objective: Recently it was shown that free recall consists of two stages: the first few recalls empty working memory and a second stage, a reactivation stage, concludes the recall. It was also shown that the serial position curve changes in mild Alzheimer’s disease – lowered total recall and lessened primacy - are similar to second stage recall and different from recall from working memory. Here we wanted to investigate whether there were any free recall first stage changes in more advanced Alzheimer’s disease. Methods: The Tarnow Unchunkable Test (TUT) uses double integer items to separate out only the first stage, the emptying of working memory, by making it difficult to reactivate items due to the lack of intra-item relationships. Results: TUT is found to be gender and culture independent with small dependencies on age and years of education. TUT 3-item test selects out diagnosed Alzheimer’s disease but not amnestic MCI or non-amnestic MCI. On average, diagnosed Alzheimer’s disease is correlated with a loss of 0.6 memory pointers (out of an average of 2.6 pointers) and this is most pronounced for the later serial positions. Conclusion: Diagnosed Alzheimer’s disease is correlated with a loss of 0.6 working memory pointers. The identification of a lost memory pointer may have implications for improved stage definitions of Alzheimer’s disease and for remediation therapy via working memory capacity management.","PeriodicalId":15012,"journal":{"name":"Journal of Alzheimers Disease & Parkinsonism","volume":"48 1","pages":"1-7"},"PeriodicalIF":0.0,"publicationDate":"2017-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89498530","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}
Pub Date : 2017-03-23DOI: 10.4172/2161-0460.1000314
Rita Chen
The pathological hallmarks of Alzheimer’s disease (AD) are the deposition of extracellular senile plaques resulting from amyloid-β (Aβ) peptide aggregation, the formation of intracellular neurofibrillary tangles composed of hyperphosphorylated tau protein, and extensive neuron death. Although 110 years have passed since the discovery of AD, the field still debates whether the amyloid hypothesis or tau hypothesis is the key issue in AD therapy. The issue of population aging makes the prevention or therapy of AD a pressing issue since the onset of this disease is highly age-correlated. Over the past two decades, the number of AD-related publications per year has grown rapidly, but to no avail. The failure rate of anti-AD clinical trials is ~99.9% and only cholinergic drugs for symptomatic control are available in the market. The success of the phase 1b clinical trial of Aducanumab immunotherapy in 2014 rekindled interest in anti-amyloid therapy, whereas the failure of the phase 3 clinical trial of Solanezumab immunotherapy once again quashed the optimism. Recently, a peptide therapy for AD was developed. A polyethylenimine (PEI) conjugated peptide, V24P(10-40)- PEI, was proposed to serve as a scavenger by trapping endogenous Aβ produced in the brain to avoid the formation of toxic aggregates. Most importantly, this peptide was given as a nose drop. After treating the AD double transgenic mice APP/PS1 with V24P(10-40)-PEI for four months, there was a significant reduction in Aβ accumulation in the brains of the treated mice. V24P(10-40)-PEI was designed to trap Aβ to interfere with its self-association, which renders Aβ more vulnerable to the attack of various endogenous Aβ-degrading enzymes.
{"title":"From Nose to Brain: The Promise of Peptide Therapy for AlzheimerâÂÂsDisease and Other Neurodegenerative Diseases","authors":"Rita Chen","doi":"10.4172/2161-0460.1000314","DOIUrl":"https://doi.org/10.4172/2161-0460.1000314","url":null,"abstract":"The pathological hallmarks of Alzheimer’s disease (AD) are the deposition of extracellular senile plaques resulting from amyloid-β (Aβ) peptide aggregation, the formation of intracellular neurofibrillary tangles composed of hyperphosphorylated tau protein, and extensive neuron death. Although 110 years have passed since the discovery of AD, the field still debates whether the amyloid hypothesis or tau hypothesis is the key issue in AD therapy. The issue of population aging makes the prevention or therapy of AD a pressing issue since the onset of this disease is highly age-correlated. Over the past two decades, the number of AD-related publications per year has grown rapidly, but to no avail. The failure rate of anti-AD clinical trials is ~99.9% and only cholinergic drugs for symptomatic control are available in the market. The success of the phase 1b clinical trial of Aducanumab immunotherapy in 2014 rekindled interest in anti-amyloid therapy, whereas the failure of the phase 3 clinical trial of Solanezumab immunotherapy once again quashed the optimism. Recently, a peptide therapy for AD was developed. A polyethylenimine (PEI) conjugated peptide, V24P(10-40)- PEI, was proposed to serve as a scavenger by trapping endogenous Aβ produced in the brain to avoid the formation of toxic aggregates. Most importantly, this peptide was given as a nose drop. After treating the AD double transgenic mice APP/PS1 with V24P(10-40)-PEI for four months, there was a significant reduction in Aβ accumulation in the brains of the treated mice. V24P(10-40)-PEI was designed to trap Aβ to interfere with its self-association, which renders Aβ more vulnerable to the attack of various endogenous Aβ-degrading enzymes.","PeriodicalId":15012,"journal":{"name":"Journal of Alzheimers Disease & Parkinsonism","volume":"17 1","pages":"1-3"},"PeriodicalIF":0.0,"publicationDate":"2017-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80179067","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}
Pub Date : 2017-03-23DOI: 10.4172/2161-0460.1000313
Panzao Yang, H. Waldvogel, C. Turner, R. Faull, M. Dragunow, J. Guan
Objective: We have previously reported vascular degeneration of human Parkinson disease (PD). In which we described degenerative pathology of endothelial cells and its association with increased string vessels in the grey matter of middle frontal gyrus (MFG). Growth factors, for example platelet-derived growth factor (PDGF), insulin-like growth factor-1 (IGF-1) and vascular endothelial growth factor (VEGF), involve in vascular remodelling by promoting cell proliferations and angiogenesis through capillary pericytes. Thus current study examined the hypothesis whether vascular degeneration in human PD is associated with impairment of vascular remodelling. Methods: Using tissue microarray method we conducted immuno histochemical staining in the grey matter of MFG of human PD (n=17) and age-matched control cases (n=17). The expression of PDGF receptor-beta, proliferating cell nuclear antigen and phosphorylation of IGF-1 receptor in capillaries, IGF binding protein-2 and VEGF were evaluated using automated image analysis software. Results: PDGF receptor-beta was specifically expressed in the pericytes which formed capillary morphology. Compared to the age-matched control cases, there were significant decrease in PDGF receptor-beta positive capillaries (p<0.05; p<0.01), proliferating vascular cells (p<0.05) and VEGF (p<0.05) in the PD cases. There no difference in phosphorylation of IGF-1 receptors, expressed in the capillaries between the groups. We found a significant increase in IGF binding protein-2, expressed in the astrocytes of PD when compared to the control cases (p<0.05). Interestingly the levels of phosphorylated IGF receptors in the capillaries were significantly correlated with the numbers of pericytes and proliferating cells in capillaries (p=0.001). Conclusion: Impaired PDGF function in the pericytes, reduced cell proliferation and VEGF suggested that the ability of vascular remodelling is impaired in PD. The maintained IGF-1 function appeared to be ineffective to retain vascular remodelling process in PD. The up-regulation of IGF binding protein-2 may suggest a role for autocrine/ paracrine of IGF-1 in PD.
{"title":"Vascular Remodelling is Impaired in Parkinson Disease","authors":"Panzao Yang, H. Waldvogel, C. Turner, R. Faull, M. Dragunow, J. Guan","doi":"10.4172/2161-0460.1000313","DOIUrl":"https://doi.org/10.4172/2161-0460.1000313","url":null,"abstract":"Objective: We have previously reported vascular degeneration of human Parkinson disease (PD). In which we described degenerative pathology of endothelial cells and its association with increased string vessels in the grey matter of middle frontal gyrus (MFG). Growth factors, for example platelet-derived growth factor (PDGF), insulin-like growth factor-1 (IGF-1) and vascular endothelial growth factor (VEGF), involve in vascular remodelling by promoting cell proliferations and angiogenesis through capillary pericytes. Thus current study examined the hypothesis whether vascular degeneration in human PD is associated with impairment of vascular remodelling. Methods: Using tissue microarray method we conducted immuno histochemical staining in the grey matter of MFG of human PD (n=17) and age-matched control cases (n=17). The expression of PDGF receptor-beta, proliferating cell nuclear antigen and phosphorylation of IGF-1 receptor in capillaries, IGF binding protein-2 and VEGF were evaluated using automated image analysis software. Results: PDGF receptor-beta was specifically expressed in the pericytes which formed capillary morphology. Compared to the age-matched control cases, there were significant decrease in PDGF receptor-beta positive capillaries (p<0.05; p<0.01), proliferating vascular cells (p<0.05) and VEGF (p<0.05) in the PD cases. There no difference in phosphorylation of IGF-1 receptors, expressed in the capillaries between the groups. We found a significant increase in IGF binding protein-2, expressed in the astrocytes of PD when compared to the control cases (p<0.05). Interestingly the levels of phosphorylated IGF receptors in the capillaries were significantly correlated with the numbers of pericytes and proliferating cells in capillaries (p=0.001). Conclusion: Impaired PDGF function in the pericytes, reduced cell proliferation and VEGF suggested that the ability of vascular remodelling is impaired in PD. The maintained IGF-1 function appeared to be ineffective to retain vascular remodelling process in PD. The up-regulation of IGF binding protein-2 may suggest a role for autocrine/ paracrine of IGF-1 in PD.","PeriodicalId":15012,"journal":{"name":"Journal of Alzheimers Disease & Parkinsonism","volume":"58 1","pages":"1-10"},"PeriodicalIF":0.0,"publicationDate":"2017-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80507941","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}
Pub Date : 2017-03-07DOI: 10.4172/2161-0460.1000311
Y. Kokubo, K. Ishii, S. Morimoto, M. Mimuro, R. Sasaki, S. Murayama, S. Kuzuhara
Background: Amyotrophic lateral sclerosis and parkinsonism-dementia complex in the Kii peninsula, Japan (Kii ALS/PDC) is an endemic and rare neurodegenerative disease. We conducted positron emission tomography (PET) study using C-11 CFT (2-b-carbomethoxy-3b-(4-fluorophenyl) tropane) and C-11 Raclopride for two patients with Kii ALS/PDC. Objective and methods: Patient #1 was 64 years old male having 12 years’ duration of the illness. Patient #2 was 68 years old female having 7 years’ duration of the illness. Results: In patient #1, CFT-PET showed marked decreased uptake in the bilateral corpus striatum, almost no signal in the posterior part of the putamen. RAC-PET showed mild decrease in the bilateral caudate nucleus and slight increase in the posterior part of the putamen. In patient #2, CFT-PET showed severe decrease in the bilateral corpus striatum, marked decrease in the posterior part of the putamen and in the caudate nucleus. RACPET showed the mild decrease in the bilateral corpus striatum. Conclusion: These results were compatible with L-dopa resistant Parkinsonism and similar to those of PSP.
{"title":"Dopaminergic Positron Emission Tomography Study on AmyotrophicLateral Sclerosis/ParkinsonismâÂÂDementia Complex in Kii, Japan","authors":"Y. Kokubo, K. Ishii, S. Morimoto, M. Mimuro, R. Sasaki, S. Murayama, S. Kuzuhara","doi":"10.4172/2161-0460.1000311","DOIUrl":"https://doi.org/10.4172/2161-0460.1000311","url":null,"abstract":"Background: Amyotrophic lateral sclerosis and parkinsonism-dementia complex in the Kii peninsula, Japan (Kii ALS/PDC) is an endemic and rare neurodegenerative disease. We conducted positron emission tomography (PET) study using C-11 CFT (2-b-carbomethoxy-3b-(4-fluorophenyl) tropane) and C-11 Raclopride for two patients with Kii ALS/PDC. Objective and methods: Patient #1 was 64 years old male having 12 years’ duration of the illness. Patient #2 was 68 years old female having 7 years’ duration of the illness. Results: In patient #1, CFT-PET showed marked decreased uptake in the bilateral corpus striatum, almost no signal in the posterior part of the putamen. RAC-PET showed mild decrease in the bilateral caudate nucleus and slight increase in the posterior part of the putamen. In patient #2, CFT-PET showed severe decrease in the bilateral corpus striatum, marked decrease in the posterior part of the putamen and in the caudate nucleus. RACPET showed the mild decrease in the bilateral corpus striatum. Conclusion: These results were compatible with L-dopa resistant Parkinsonism and similar to those of PSP.","PeriodicalId":15012,"journal":{"name":"Journal of Alzheimers Disease & Parkinsonism","volume":"24 1","pages":"1-3"},"PeriodicalIF":0.0,"publicationDate":"2017-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82285553","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}
Pub Date : 2017-02-28DOI: 10.4172/2161-0460.1000307
Y. Qiao, Dantao Peng, M. Jin, Shuang Xue
Aim: We reported a family with a presenilin 1 (PSEN1) gene mutation whose clinical manifestations are similar to the Dementia with Lewy bodies. Methods: We collected peripheral blood of the proband, his daughter and 100 normal Chinese individuals and extracted genomic DNAi¼PCR-sequencing of PSEN1 and microtubule associated protein tau (MAPT) were performed.We also gave them transcranial sonography test (TCS). Results: We found that the proband and his daughter were heterozygous for a mutation 1292nd base in exon 12 of PSEN1, causing the amino acid alanine substituded by valine at codon 431 (A431V), but this was not found in normal controlsi¼Meanwhile hyperechogenicity of bilateral substantia nigra could be seen in the two patients with the right-left asymmetry index >1.15. Conclusion: This study identified a mutation A431V in the PSEN1 gene in Chinese patients. We considered it might play an important role in familial Alzheimer’s disease leading clinical manifestations similar to DLB.
{"title":"Presenilin 1 Mutation (A431V) Causing Features of Dementia with LewyBodies in a Chinese Family of AlzheimerâÂÂs Disease","authors":"Y. Qiao, Dantao Peng, M. Jin, Shuang Xue","doi":"10.4172/2161-0460.1000307","DOIUrl":"https://doi.org/10.4172/2161-0460.1000307","url":null,"abstract":"Aim: We reported a family with a presenilin 1 (PSEN1) gene mutation whose clinical manifestations are similar to the Dementia with Lewy bodies. Methods: We collected peripheral blood of the proband, his daughter and 100 normal Chinese individuals and extracted genomic DNAi¼PCR-sequencing of PSEN1 and microtubule associated protein tau (MAPT) were performed.We also gave them transcranial sonography test (TCS). Results: We found that the proband and his daughter were heterozygous for a mutation 1292nd base in exon 12 of PSEN1, causing the amino acid alanine substituded by valine at codon 431 (A431V), but this was not found in normal controlsi¼Meanwhile hyperechogenicity of bilateral substantia nigra could be seen in the two patients with the right-left asymmetry index >1.15. Conclusion: This study identified a mutation A431V in the PSEN1 gene in Chinese patients. We considered it might play an important role in familial Alzheimer’s disease leading clinical manifestations similar to DLB.","PeriodicalId":15012,"journal":{"name":"Journal of Alzheimers Disease & Parkinsonism","volume":"2 1","pages":"1-4"},"PeriodicalIF":0.0,"publicationDate":"2017-02-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78888504","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}
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