The respiratory infectious disease COVID-19, which emerged in 2019, has affected the world population over a brief period. In 2020, the disease was declared a pandemic by the World Health Organization. Although most COVID-19 patients primarily develop respiratory symptoms, neurological symptoms have been observed. Neurological symptoms are usually mild and non-specific. However, some patients could experience life-threatening neurological symptoms. With the increase in the incidence of COVID-19, the disease spectrum of patients with central and peripheral nervous system involvement has expanded significantly compared to the previous period. Lack of awareness has caused delays in diagnosis and treatment; therefore, updating the disease spectrum of neurological complications of COVID-19 is necessary. After COVID-19 claimed millions of lives, researchers found that some vaccines may induce autoimmune inflammatory responses in the nervous system via molecular mimicry, leading to SARS-CoV-2 vaccine-related neurological deficits. These neurological complications are often ignored by clinicians, delaying diagnosis and treatment; it is essential to study cases of vaccine-associated neurological complications. Therefore, we summarize the neurological complications of COVID-19 and nervous system adverse reactions caused by SARS-CoV-2 vaccines to help clinicians and public health service personnel understand these rare complications. Avoiding delays in diagnosis and treatment would ensure the safety of COVID-19 patients and SARS-CoV-2 vaccine recipients.
{"title":"Neurological complications of COVID-19 and SARS-CoV-2 vaccination: an update","authors":"Huan-yu Meng, Qinming Zhou, Sheng Chen","doi":"10.20517/and.2022.29","DOIUrl":"https://doi.org/10.20517/and.2022.29","url":null,"abstract":"The respiratory infectious disease COVID-19, which emerged in 2019, has affected the world population over a brief period. In 2020, the disease was declared a pandemic by the World Health Organization. Although most COVID-19 patients primarily develop respiratory symptoms, neurological symptoms have been observed. Neurological symptoms are usually mild and non-specific. However, some patients could experience life-threatening neurological symptoms. With the increase in the incidence of COVID-19, the disease spectrum of patients with central and peripheral nervous system involvement has expanded significantly compared to the previous period. Lack of awareness has caused delays in diagnosis and treatment; therefore, updating the disease spectrum of neurological complications of COVID-19 is necessary. After COVID-19 claimed millions of lives, researchers found that some vaccines may induce autoimmune inflammatory responses in the nervous system via molecular mimicry, leading to SARS-CoV-2 vaccine-related neurological deficits. These neurological complications are often ignored by clinicians, delaying diagnosis and treatment; it is essential to study cases of vaccine-associated neurological complications. Therefore, we summarize the neurological complications of COVID-19 and nervous system adverse reactions caused by SARS-CoV-2 vaccines to help clinicians and public health service personnel understand these rare complications. Avoiding delays in diagnosis and treatment would ensure the safety of COVID-19 patients and SARS-CoV-2 vaccine recipients.","PeriodicalId":93251,"journal":{"name":"Ageing and neurodegenerative diseases","volume":"81 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90249941","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}
Min Xiong, Honglu Yu, Ye Tian, Lanxia Meng, Zhentao Zhang
Alzheimer’s disease (AD) is the most common neurodegenerative disease, which is characterized by the deposition of senile plaques composed of amyloid-β (Aβ) and neurofibrillary tangles (NFTs) composed of hyperphosphorylated tau. Currently, the underlying cellular and molecular mechanisms of AD are still unclear. Growing evidence suggests that pathogen infections prominently promote the development of AD pathology. In this article, we reviewed the effect of multiple infectious pathogens that contribute to AD pathogenesis. Pathogens such as bacteria, viruses, and fungi are detected in the brains of AD patients and are known to be able to promote the development of AD pathology, including Aβ deposition and the formation of tau tangles. Here, we summarized the infectious pathogen-associated mechanisms of AD and provided new insight into the anti-infection remedy for AD.
{"title":"Pathogen infection in Alzheimer’s disease: pathophysiology and therapeutic strategies","authors":"Min Xiong, Honglu Yu, Ye Tian, Lanxia Meng, Zhentao Zhang","doi":"10.20517/and.2022.32","DOIUrl":"https://doi.org/10.20517/and.2022.32","url":null,"abstract":"Alzheimer’s disease (AD) is the most common neurodegenerative disease, which is characterized by the deposition of senile plaques composed of amyloid-β (Aβ) and neurofibrillary tangles (NFTs) composed of hyperphosphorylated tau. Currently, the underlying cellular and molecular mechanisms of AD are still unclear. Growing evidence suggests that pathogen infections prominently promote the development of AD pathology. In this article, we reviewed the effect of multiple infectious pathogens that contribute to AD pathogenesis. Pathogens such as bacteria, viruses, and fungi are detected in the brains of AD patients and are known to be able to promote the development of AD pathology, including Aβ deposition and the formation of tau tangles. Here, we summarized the infectious pathogen-associated mechanisms of AD and provided new insight into the anti-infection remedy for AD.","PeriodicalId":93251,"journal":{"name":"Ageing and neurodegenerative diseases","volume":"115 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79243528","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}
Mitochondrial dysfunction can lead to degeneration in the central nervous system. F1Fo-ATPase catalyzes most of the intracellular ATP synthesis which plays an essential role in cellular energy supply. The dimerized assembly of F1Fo-ATPase underlies the rotational catalytic function and regulates the mechanisms of oxidative phosphorylation. F1Fo-ATPase dysfunction is involved in a variety of neurological diseases, including epilepsy, Alzheimer's disease, and Parkinson’s disease. Dysregulated expression, activity, and localization of F1Fo-ATPase subunits and the interactions with pathogenic proteins result in decreased F1Fo-ATPase activity and ATP production, and aggravated oxidative stress.
{"title":"The role of domain alterations in F1Fo-ATPase dysfunction associated to neurodegenerative diseases","authors":"Miaomiao Zhou, Yuwan Lin, Zhiling Zhang, Yuting Tang, Wenlong Zhang, Hanqun Liu, Guoyou Peng, Jiewen Qiu, Wenyuan Guo, Xiang Chen, P. Xu","doi":"10.20517/and.2022.28","DOIUrl":"https://doi.org/10.20517/and.2022.28","url":null,"abstract":"Mitochondrial dysfunction can lead to degeneration in the central nervous system. F1Fo-ATPase catalyzes most of the intracellular ATP synthesis which plays an essential role in cellular energy supply. The dimerized assembly of F1Fo-ATPase underlies the rotational catalytic function and regulates the mechanisms of oxidative phosphorylation. F1Fo-ATPase dysfunction is involved in a variety of neurological diseases, including epilepsy, Alzheimer's disease, and Parkinson’s disease. Dysregulated expression, activity, and localization of F1Fo-ATPase subunits and the interactions with pathogenic proteins result in decreased F1Fo-ATPase activity and ATP production, and aggravated oxidative stress.","PeriodicalId":93251,"journal":{"name":"Ageing and neurodegenerative diseases","volume":"40 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85825610","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}
Parkinson’s disease (PD) is an age-related neurodegenerative disease mainly affecting the elderly population. Despite recent progresses in pharmacologic therapies and surgical interventions such as deep brain stimulation, current PD therapies are limited to relieving disease symptoms rather than stopping disease progression, highlighting an urgent yet unmet need for disease-modifying interventions. Neuroinflammation has been proposed as a pivotal contributing factor that drives the initiation and progression of PD pathology. Owing to the revolution in disease-modifying drugs (DMDs) that successfully change the course of multiple sclerosis (MS), a central nervous system inflammatory autoimmune disease, it has become tempting to repurpose MS DMDs as new treatment options for PD. This review summarizes the ongoing and completed studies of MS DMDs in PD as a potential opportunity to address this unmet need. Future clinical trials are warranted to further evaluate the efficacy of DMDs in patients with PD.
{"title":"Repurposing multiples sclerosis disease-modifying drugs for Parkinson's disease","authors":"Tingyu Cao, Qiang Liu, Xiaodong Zhu","doi":"10.20517/and.2023.08","DOIUrl":"https://doi.org/10.20517/and.2023.08","url":null,"abstract":"Parkinson’s disease (PD) is an age-related neurodegenerative disease mainly affecting the elderly population. Despite recent progresses in pharmacologic therapies and surgical interventions such as deep brain stimulation, current PD therapies are limited to relieving disease symptoms rather than stopping disease progression, highlighting an urgent yet unmet need for disease-modifying interventions. Neuroinflammation has been proposed as a pivotal contributing factor that drives the initiation and progression of PD pathology. Owing to the revolution in disease-modifying drugs (DMDs) that successfully change the course of multiple sclerosis (MS), a central nervous system inflammatory autoimmune disease, it has become tempting to repurpose MS DMDs as new treatment options for PD. This review summarizes the ongoing and completed studies of MS DMDs in PD as a potential opportunity to address this unmet need. Future clinical trials are warranted to further evaluate the efficacy of DMDs in patients with PD.","PeriodicalId":93251,"journal":{"name":"Ageing and neurodegenerative diseases","volume":"207 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89202488","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}
Xinyue Deng, Wen Zheng, Yan Yang, Zhijian Yang, Huan Li, Zhi Song, Jiangang Wang, H. Deng, L. Yuan
Parkinson’s disease (PD) is a clinical syndrome and a heterogeneous group of neurodegenerative conditions with variable pathologies and clinical sub-entities, characterized by motor symptoms and non-motor features. PD represents an outcome of the combination of genes and other risk or protective factors. Patients with variants in the phospholipase A2 group VI gene (PLA2G6) can present complex Parkinsonian phenotypes. This study reported a PD patient with typical motor symptoms of PD, including bradykinesia, gait disturbance, rigidity, and rest tremor, who also suffered from nocturia, constipation, and sleeping problems. Two PLA2G6 variants, c.402C>T and c.2327_2328del, were identified in the patient by whole exome sequencing followed by Sanger sequencing. The transition c.402C>T was predicted to generate an alternative acceptor splice site, though the minigene splicing assay showed negative in vitro outcomes. The novel variant c.2327_2328del was predicted to result in a truncated protein. These two variants may be pathogenic in PD or increase the susceptibility to PD individually or collaboratively. This discovery may enrich the genetic landscape of PLA2G6-associated PD and confirm the notion of prioritizing whole exome sequencing analysis in patients with PD.
{"title":"Identification of PLA2G6 variants in a Chinese patient with Parkinson's disease","authors":"Xinyue Deng, Wen Zheng, Yan Yang, Zhijian Yang, Huan Li, Zhi Song, Jiangang Wang, H. Deng, L. Yuan","doi":"10.20517/and.2023.06","DOIUrl":"https://doi.org/10.20517/and.2023.06","url":null,"abstract":"Parkinson’s disease (PD) is a clinical syndrome and a heterogeneous group of neurodegenerative conditions with variable pathologies and clinical sub-entities, characterized by motor symptoms and non-motor features. PD represents an outcome of the combination of genes and other risk or protective factors. Patients with variants in the phospholipase A2 group VI gene (PLA2G6) can present complex Parkinsonian phenotypes. This study reported a PD patient with typical motor symptoms of PD, including bradykinesia, gait disturbance, rigidity, and rest tremor, who also suffered from nocturia, constipation, and sleeping problems. Two PLA2G6 variants, c.402C>T and c.2327_2328del, were identified in the patient by whole exome sequencing followed by Sanger sequencing. The transition c.402C>T was predicted to generate an alternative acceptor splice site, though the minigene splicing assay showed negative in vitro outcomes. The novel variant c.2327_2328del was predicted to result in a truncated protein. These two variants may be pathogenic in PD or increase the susceptibility to PD individually or collaboratively. This discovery may enrich the genetic landscape of PLA2G6-associated PD and confirm the notion of prioritizing whole exome sequencing analysis in patients with PD.","PeriodicalId":93251,"journal":{"name":"Ageing and neurodegenerative diseases","volume":"12 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87246076","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}
Neurodegenerative disorders represent a group of aging-related diseases affecting the different parts of the central nervous system. Axonal degeneration is among the leading causes of morbidity and disease progression in Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and other neurogenerative disorders. The unique structures of axons may make them particularly vulnerable to internal homeostasis. The axonal endoplasmic reticulum (ER) has emerged as one of the most important hallmarks in those neurodegenerative disorders associated with dysfunction of axonal transport, lipid synthesis, calcium dynamics, and interactions with other organelles. In this review, we summarize the role of tubular ER and its resident proteins in axonal degeneration, which emerges as an early pathological event in the axonal degeneration process. We also discuss the potential relationship between autophagy and tubular ER. With this review, we can consolidate the recent research advances in the role of tubular ER in axonal degeneration associated with several major neurodegenerative disorders and improve our understanding of axon pathophysiology and potential target therapies.
{"title":"The role of the tubular endoplasmic reticulum in the axonal degeneration associated with neurodegenerative disorders","authors":"Panpan Wang, Murad Al-Nusaif, Weidong Le","doi":"10.20517/and.2023.12","DOIUrl":"https://doi.org/10.20517/and.2023.12","url":null,"abstract":"Neurodegenerative disorders represent a group of aging-related diseases affecting the different parts of the central nervous system. Axonal degeneration is among the leading causes of morbidity and disease progression in Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and other neurogenerative disorders. The unique structures of axons may make them particularly vulnerable to internal homeostasis. The axonal endoplasmic reticulum (ER) has emerged as one of the most important hallmarks in those neurodegenerative disorders associated with dysfunction of axonal transport, lipid synthesis, calcium dynamics, and interactions with other organelles. In this review, we summarize the role of tubular ER and its resident proteins in axonal degeneration, which emerges as an early pathological event in the axonal degeneration process. We also discuss the potential relationship between autophagy and tubular ER. With this review, we can consolidate the recent research advances in the role of tubular ER in axonal degeneration associated with several major neurodegenerative disorders and improve our understanding of axon pathophysiology and potential target therapies.","PeriodicalId":93251,"journal":{"name":"Ageing and neurodegenerative diseases","volume":"19 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82546867","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}
In Parkinson's disease (PD), the accumulation of misfolded α-synuclein (α-syn) in the brain is a major characteristic of the pathology. α-Syn formation and aggregation may originate in the enteric nervous system and pathologic α-syn can be transmitted to the central nervous system via the vagus nerve. In this commentary, we summarize the findings of Yang et al.[1] in which they report on the ability of a Parkinson’s disease patient's intestinal and vagus lysates containing pathologic α-syn to template endogenous rat α-syn culminating in the spread of pathologic α-syn, deposition of pathologic α-syn, and neuroinflammation in different brain regions and neurodegeneration of dopamine neurons. These observations are discussed with other studies supporting the significance of the gastrointestinal system in PD pathogenesis and future directions of research are highlighted.
{"title":"A new Perspective on Parkinson's disease: exploring the involvement of intestine and vagus lysates in α-synucleinopathy propagation","authors":"R. Ullah, V. Dawson, T. Dawson","doi":"10.20517/and.2023.07","DOIUrl":"https://doi.org/10.20517/and.2023.07","url":null,"abstract":"In Parkinson's disease (PD), the accumulation of misfolded α-synuclein (α-syn) in the brain is a major characteristic of the pathology. α-Syn formation and aggregation may originate in the enteric nervous system and pathologic α-syn can be transmitted to the central nervous system via the vagus nerve. In this commentary, we summarize the findings of Yang et al.[1] in which they report on the ability of a Parkinson’s disease patient's intestinal and vagus lysates containing pathologic α-syn to template endogenous rat α-syn culminating in the spread of pathologic α-syn, deposition of pathologic α-syn, and neuroinflammation in different brain regions and neurodegeneration of dopamine neurons. These observations are discussed with other studies supporting the significance of the gastrointestinal system in PD pathogenesis and future directions of research are highlighted.","PeriodicalId":93251,"journal":{"name":"Ageing and neurodegenerative diseases","volume":"25 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74443996","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}
Parkinson’s disease (PD) is a common neurodegenerative disease, pathologically characterized by the progressive degeneration of dopaminergic neurons in the substantia nigra. Although various biomarkers and imaging criteria for PD have been established, objective and reliable evaluation methods are still lacking. Electroneurography, as an objective measurement of evoked compound muscle action potentials, is used to assess the integrity of the peripheral nerve and is important in the diagnosis and differential diagnosis of PD with neuromuscular injury. Moreover, it provides references for the evaluation and quantification of the motor function in PD. Here, we summarize recent advances in clinical research of electroneurography in PD, including the peripheral nerve conduction velocity, needle electromyography, surface electromyography, and motion unit number estimation. The potential values of electroneurography in PD diagnosis are also involved.
{"title":"Electroneurography abnormality in Parkinson’s disease: a potential biomarker to help diagnosis","authors":"Yiying Hu","doi":"10.20517/and.2022.04","DOIUrl":"https://doi.org/10.20517/and.2022.04","url":null,"abstract":"Parkinson’s disease (PD) is a common neurodegenerative disease, pathologically characterized by the progressive degeneration of dopaminergic neurons in the substantia nigra. Although various biomarkers and imaging criteria for PD have been established, objective and reliable evaluation methods are still lacking. Electroneurography, as an objective measurement of evoked compound muscle action potentials, is used to assess the integrity of the peripheral nerve and is important in the diagnosis and differential diagnosis of PD with neuromuscular injury. Moreover, it provides references for the evaluation and quantification of the motor function in PD. Here, we summarize recent advances in clinical research of electroneurography in PD, including the peripheral nerve conduction velocity, needle electromyography, surface electromyography, and motion unit number estimation. The potential values of electroneurography in PD diagnosis are also involved.","PeriodicalId":93251,"journal":{"name":"Ageing and neurodegenerative diseases","volume":"13 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85218528","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}
Li Jiang, Xiao-yu Liu, Xiao-Qin Yan, Yu-Hui Liu, Yan-Jiang Wang, Ying Yang, Ling-Ru Wang
Aim: With the increasing number of patients recovered from COVID-19, the long-term health consequences of this disease have attracted much attention. Neurological complications are commonly seen in the acute phase of COVID-19, especially in older adults. This study aimed to investigate the long-term neurological sequelae in older COVID-19 survivors. Methods: A total of 1438 COVID-19 survivors were recruited in this study. One year after hospital discharge, information about self-reported symptoms of the central and peripheral nervous system was collected. Comparisons of these neurological symptoms between COVID-19 survivors with severe and nonsevere cases were performed. Results: A total of 139 (53.46%) COVID-19 survivors with severe cases and 328 (27.84%) survivors with nonsevere cases reported at least one neurological symptom one year after discharge. Most of these neurological symptoms were symptoms of the central nervous system. Specifically, 126 (48.46%) survivors with severe cases and 306 (25.98%) survivors with nonsevere cases reported at least one CNS symptom. The most frequently reported symptoms were memory deficit [234 (16.27%)] and attention deficit [80 (5.56%)]. Disease severity was associated with increased risks of long-term neurological sequelae of COVID-19. Conclusion: This study demonstrated that neurological sequelae of COVID-19 are common one year after patient discharge, suggesting that the effects of COVID-19 on the neurological system are prolonged.
{"title":"One-year self-reported neurological sequelae in older COVID-19 survivors","authors":"Li Jiang, Xiao-yu Liu, Xiao-Qin Yan, Yu-Hui Liu, Yan-Jiang Wang, Ying Yang, Ling-Ru Wang","doi":"10.20517/and.2022.10","DOIUrl":"https://doi.org/10.20517/and.2022.10","url":null,"abstract":"Aim: With the increasing number of patients recovered from COVID-19, the long-term health consequences of this disease have attracted much attention. Neurological complications are commonly seen in the acute phase of COVID-19, especially in older adults. This study aimed to investigate the long-term neurological sequelae in older COVID-19 survivors. Methods: A total of 1438 COVID-19 survivors were recruited in this study. One year after hospital discharge, information about self-reported symptoms of the central and peripheral nervous system was collected. Comparisons of these neurological symptoms between COVID-19 survivors with severe and nonsevere cases were performed. Results: A total of 139 (53.46%) COVID-19 survivors with severe cases and 328 (27.84%) survivors with nonsevere cases reported at least one neurological symptom one year after discharge. Most of these neurological symptoms were symptoms of the central nervous system. Specifically, 126 (48.46%) survivors with severe cases and 306 (25.98%) survivors with nonsevere cases reported at least one CNS symptom. The most frequently reported symptoms were memory deficit [234 (16.27%)] and attention deficit [80 (5.56%)]. Disease severity was associated with increased risks of long-term neurological sequelae of COVID-19. Conclusion: This study demonstrated that neurological sequelae of COVID-19 are common one year after patient discharge, suggesting that the effects of COVID-19 on the neurological system are prolonged.","PeriodicalId":93251,"journal":{"name":"Ageing and neurodegenerative diseases","volume":"76 6 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83469628","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 : 2022-01-01Epub Date: 2022-04-27DOI: 10.20517/and.2022.07
Jia Yu, Carmelo Sgobio, Xuan Yang, Yu Peng, Xi Chen, Lixin Sun, Hoon Shim, Huaibin Cai
Aim: Missense mutations of dynactin subunit p150Glued have been associated with multiple neurodegenerative diseases, including Perry syndrome, characterized by inherited parkinsonism, depression, weight loss, and hypoventilation. The current study investigated how the pathogenic mutant p150Glued affects the integrity and function of the nigrostriatal dopaminergic (DA) pathway in vivo.
Methods: Using a tetracycline-controlled transcriptional regulation system, transgenic mouse models were generated with selective overexpression of wild-type, motor neuron disease-related G59S mutant, or Perry syndrome-related G71R mutant human p150Glued in midbrain DA neurons. A series of behavioral, neuropathological, neurochemical, electrochemical, and biochemical studies were performed on the mice to examine and compare the pathogenic impact of the two mutant p150Glued on the survival and function of midbrain DA neurons.
Results: Compared with non-transgenic control mice, transgenic mice overexpressing wild-type human p150Glued showed neither motor phenotypes nor pathological, functional, or biochemical abnormalities of the nigrostriatal DA pathway. Transgenic mice overexpressing G59S mutant p150Glued displayed weight loss, motor deficits, early-onset defects in dopamine transmission, and early-onset loss of DA neurons and axons. Transgenic mice overexpressing G71R p150Glued mutant exhibited hyperactivities, impaired motor coordination, early-onset dysfunction of dopamine uptake, and late-onset loss of DA neurons and axons. In addition, overexpression of either G59S or G71R mutant p150Glued in midbrain DA neurons preferentially downregulated the expression of dopamine transporter at dopaminergic axon terminals. Furthermore, G59S mutant p150Glued rather than G71R mutant p150Glued formed aggregates in midbrain DA neurons in vivo, and the aggregates trapped dynein/dynactin, co-localized with lysosomes, and upregulated ubiquitination.
Conclusion: These findings demonstrate that selective expression of either G59S or G71R mutant p150Glued in mouse midbrain DA neurons leads to progressive degeneration of the nigrostriatal DA pathway and indicate that G59S and G71R mutant p150Glued exhibit differential pathogenic impact on the survival and function of midbrain DA neurons in vivo.
{"title":"Selective expression of neurodegenerative diseases-related mutant p150<sup>Glued</sup> in midbrain dopaminergic neurons causes progressive degeneration of nigrostriatal pathway.","authors":"Jia Yu, Carmelo Sgobio, Xuan Yang, Yu Peng, Xi Chen, Lixin Sun, Hoon Shim, Huaibin Cai","doi":"10.20517/and.2022.07","DOIUrl":"10.20517/and.2022.07","url":null,"abstract":"<p><strong>Aim: </strong>Missense mutations of dynactin subunit p150<sup>Glued</sup> have been associated with multiple neurodegenerative diseases, including Perry syndrome, characterized by inherited parkinsonism, depression, weight loss, and hypoventilation. The current study investigated how the pathogenic mutant p150<sup>Glued</sup> affects the integrity and function of the nigrostriatal dopaminergic (DA) pathway <i>in vivo</i>.</p><p><strong>Methods: </strong>Using a tetracycline-controlled transcriptional regulation system, transgenic mouse models were generated with selective overexpression of wild-type, motor neuron disease-related G59S mutant, or Perry syndrome-related G71R mutant human p150<sup>Glued</sup> in midbrain DA neurons. A series of behavioral, neuropathological, neurochemical, electrochemical, and biochemical studies were performed on the mice to examine and compare the pathogenic impact of the two mutant p150<sup>Glued</sup> on the survival and function of midbrain DA neurons.</p><p><strong>Results: </strong>Compared with non-transgenic control mice, transgenic mice overexpressing wild-type human p150<sup>Glued</sup> showed neither motor phenotypes nor pathological, functional, or biochemical abnormalities of the nigrostriatal DA pathway. Transgenic mice overexpressing G59S mutant p150<sup>Glued</sup> displayed weight loss, motor deficits, early-onset defects in dopamine transmission, and early-onset loss of DA neurons and axons. Transgenic mice overexpressing G71R p150<sup>Glued</sup> mutant exhibited hyperactivities, impaired motor coordination, early-onset dysfunction of dopamine uptake, and late-onset loss of DA neurons and axons. In addition, overexpression of either G59S or G71R mutant p150<sup>Glued</sup> in midbrain DA neurons preferentially downregulated the expression of dopamine transporter at dopaminergic axon terminals. Furthermore, G59S mutant p150<sup>Glued</sup> rather than G71R mutant p150<sup>Glued</sup> formed aggregates in midbrain DA neurons <i>in vivo</i>, and the aggregates trapped dynein/dynactin, co-localized with lysosomes, and upregulated ubiquitination.</p><p><strong>Conclusion: </strong>These findings demonstrate that selective expression of either G59S or G71R mutant p150<sup>Glued</sup> in mouse midbrain DA neurons leads to progressive degeneration of the nigrostriatal DA pathway and indicate that G59S and G71R mutant p150<sup>Glued</sup> exhibit differential pathogenic impact on the survival and function of midbrain DA neurons <i>in vivo</i>.</p>","PeriodicalId":93251,"journal":{"name":"Ageing and neurodegenerative diseases","volume":"9 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2022-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12797871/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90726183","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}
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