Rett syndrome (RTT) is a neurodevelopmental disorder primarily caused by mutations in the MECP2 gene. Neuronal damage is the main factor contributing to RTT, and the loss of MeCP2 function can result in reduced neuronal somas size, decreased dendritic abundance, and impaired neuronal function. While specific restoration of MeCP2 expression in neurons has been reported to partially rescue the behavioral phenotype and prolong the lifespan of mice, it cannot provide a complete cure. Therefore, other cells may be involved in the development of RTT. Although imaging and autopsy findings have revealed decreased white matter volume and corpus callosum thickness in RTT patients, the mechanisms underlying the development of white matter abnormalities remain unclear. These abnormalities are predominantly caused by damage to mature oligodendrocytes. This review provides an overview of the proliferation, differentiation, and function of oligodendrocyte lineage cells and elucidates the role of MeCP2 in these cells.
{"title":"Role of MeCP2 in oligodendrocyte lineage cells in Rett syndrome: review and inference","authors":"Zhen Zhang, Peng Li, Yongchang Chen","doi":"10.20517/and.2023.13","DOIUrl":"https://doi.org/10.20517/and.2023.13","url":null,"abstract":"Rett syndrome (RTT) is a neurodevelopmental disorder primarily caused by mutations in the MECP2 gene. Neuronal damage is the main factor contributing to RTT, and the loss of MeCP2 function can result in reduced neuronal somas size, decreased dendritic abundance, and impaired neuronal function. While specific restoration of MeCP2 expression in neurons has been reported to partially rescue the behavioral phenotype and prolong the lifespan of mice, it cannot provide a complete cure. Therefore, other cells may be involved in the development of RTT. Although imaging and autopsy findings have revealed decreased white matter volume and corpus callosum thickness in RTT patients, the mechanisms underlying the development of white matter abnormalities remain unclear. These abnormalities are predominantly caused by damage to mature oligodendrocytes. This review provides an overview of the proliferation, differentiation, and function of oligodendrocyte lineage cells and elucidates the role of MeCP2 in these cells.","PeriodicalId":93251,"journal":{"name":"Ageing and neurodegenerative diseases","volume":"22 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-07-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89765649","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 the past decade, significant advancements have been made in understanding the brain regions and neuronal circuits regulating neurological behaviors. The endocannabinoid (eCB) system, which is ubiquitously distributed in the brain and extensively involved in synaptic modulation, has been believed to play potential roles in neuronal circuit processes and related disorders. Although eCB-based pharmacological studies have made some clinical achievements, they still often encounter conflicting reports or undesired effects due to global manipulation of manifold brain regions and neuronal circuits, which impede the therapeutic application of eCB-based medications. In this review, we are devoted to discussing the versatile forms of eCB-mediated synaptic plasticity and dissecting currently well-studied specific cannabinoid circuits involved in behavioral domains which are closely linked to the organism’s survival and life quality, such as pain perception and stress-related emotion disorders. By gaining new insights into selective cannabinoid control in circuits, we can potentially mitigate the drawbacks of traditional pharmacology and facilitate the development of precision medicine with novel therapeutic strategies and drug discoveries.
{"title":"Cannabinoid modulations of pain- and stress-related circuits","authors":"Ying Wang, Qingyu Wang, Li Tang, Xia Zhang","doi":"10.20517/and.2023.19","DOIUrl":"https://doi.org/10.20517/and.2023.19","url":null,"abstract":"In the past decade, significant advancements have been made in understanding the brain regions and neuronal circuits regulating neurological behaviors. The endocannabinoid (eCB) system, which is ubiquitously distributed in the brain and extensively involved in synaptic modulation, has been believed to play potential roles in neuronal circuit processes and related disorders. Although eCB-based pharmacological studies have made some clinical achievements, they still often encounter conflicting reports or undesired effects due to global manipulation of manifold brain regions and neuronal circuits, which impede the therapeutic application of eCB-based medications. In this review, we are devoted to discussing the versatile forms of eCB-mediated synaptic plasticity and dissecting currently well-studied specific cannabinoid circuits involved in behavioral domains which are closely linked to the organism’s survival and life quality, such as pain perception and stress-related emotion disorders. By gaining new insights into selective cannabinoid control in circuits, we can potentially mitigate the drawbacks of traditional pharmacology and facilitate the development of precision medicine with novel therapeutic strategies and drug discoveries.","PeriodicalId":93251,"journal":{"name":"Ageing and neurodegenerative diseases","volume":"8 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79381757","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}
Alpha-synuclein (α-syn) is a presynaptic and nuclear protein that has been inextricably linked to Parkinson’s disease (PD). It regulates the presynaptic activities of neurons, but its aggregation and spreading have been associated with a group of diseases termed synucleinopathies. Here, we examined the commonly held view that α-syn caused disease and explored the concept that α-syn aggregation may be a consequence of pathobiology. Future therapies may need to encompass α-syn both a cause and consequence of the disease process.
{"title":"Can alpha-synuclein be both the cause and a consequence of Parkinson's disease?","authors":"Kang Chen, Yu-jie Guo, P. Lei, D. Finkelstein","doi":"10.20517/and.2023.05","DOIUrl":"https://doi.org/10.20517/and.2023.05","url":null,"abstract":"Alpha-synuclein (α-syn) is a presynaptic and nuclear protein that has been inextricably linked to Parkinson’s disease (PD). It regulates the presynaptic activities of neurons, but its aggregation and spreading have been associated with a group of diseases termed synucleinopathies. Here, we examined the commonly held view that α-syn caused disease and explored the concept that α-syn aggregation may be a consequence of pathobiology. Future therapies may need to encompass α-syn both a cause and consequence of the disease process.","PeriodicalId":93251,"journal":{"name":"Ageing and neurodegenerative diseases","volume":"82 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"91183404","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}
Cai Huimin, Fu Xiaofeng, Quan Shuiyue, Ren Ziye, Chu Changbiao, Jia Longfei
Alzheimer’s disease (AD) is common and devastating. However, current symptomatic treatments are unable to alter the progression of the disease. Fortunately, many ongoing trials of disease-modifying therapies may provide new insights into the treatment and prevention of AD. Due to the long-held amyloid cascade hypothesis, the development of pharmacotherapies targeting amyloid-β (Aβ) has been a major focus in AD research. The recent positive results and approval of several anti- Aβ monoclonal antibodies seem to be a milestone for AD treatment. In this review, we highlight the rationale and status of different Aβ-targeted therapies for AD, including those now on the market and those in clinical trials. We also discuss the challenges and future perspectives of Aβ-targeted therapies for AD.
阿尔茨海默病(AD)是一种常见且具有破坏性的疾病。然而，目前的对症治疗无法改变疾病的进展。幸运的是，许多正在进行的疾病改善疗法的试验可能为阿尔茨海默病的治疗和预防提供新的见解。由于长期以来的淀粉样蛋白级联假说，针对淀粉样蛋白β (a β)的药物治疗的开发一直是阿尔茨海默病研究的主要焦点。最近一些抗a β单克隆抗体的阳性结果和批准似乎是AD治疗的一个里程碑。在这篇综述中，我们重点介绍了不同的a β靶向治疗AD的基本原理和现状，包括那些已经上市的和正在临床试验的治疗方法。我们还讨论了a β靶向治疗AD的挑战和未来前景。
{"title":"Amyloid-β-targeted therapies for Alzheimer's disease: currently and in the future","authors":"Cai Huimin, Fu Xiaofeng, Quan Shuiyue, Ren Ziye, Chu Changbiao, Jia Longfei","doi":"10.20517/and.2023.16","DOIUrl":"https://doi.org/10.20517/and.2023.16","url":null,"abstract":"Alzheimer’s disease (AD) is common and devastating. However, current symptomatic treatments are unable to alter the progression of the disease. Fortunately, many ongoing trials of disease-modifying therapies may provide new insights into the treatment and prevention of AD. Due to the long-held amyloid cascade hypothesis, the development of pharmacotherapies targeting amyloid-β (Aβ) has been a major focus in AD research. The recent positive results and approval of several anti- Aβ monoclonal antibodies seem to be a milestone for AD treatment. In this review, we highlight the rationale and status of different Aβ-targeted therapies for AD, including those now on the market and those in clinical trials. We also discuss the challenges and future perspectives of Aβ-targeted therapies for AD.","PeriodicalId":93251,"journal":{"name":"Ageing and neurodegenerative diseases","volume":"31 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"135698923","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}
Increasing lines of evidence have indicated the beneficial impacts of exercise on the neurodegeneration and cognitive decline of Alzheimer’s disease (AD). While general mechanisms underlying the positive effects, including the elevated neurotrophins level, improved neurogenesis and neuroplasticity, restored angiogenesis and autophagy, and reduced neuroinflammation, have been well documented, the epigenetic mechanisms of exercise on AD, however, are still inconclusive. Exercise can regulate the expression of those AD-related genes or proteins through various epigenetic modulations, thereafter rescuing AD pathologies and improving cognitive deficits of AD. In this review, we briefly summarized recent research advances in the beneficial impacts of exercise on cognition and AD and discussed the underlying mechanisms from an epigenetic point of view, including DNA methylation, histone modifications, and non-coding RNAs. A deep understanding of how exercise epigenetically promotes cognitive and pathological recoveries in AD is crucial for the future discovery of precise exercise procedures or exercise-like remedies to treat this disease.
{"title":"Benefits of physical exercise on Alzheimer's disease: an epigenetic view","authors":"Song Li","doi":"10.20517/and.2022.37","DOIUrl":"https://doi.org/10.20517/and.2022.37","url":null,"abstract":"Increasing lines of evidence have indicated the beneficial impacts of exercise on the neurodegeneration and cognitive decline of Alzheimer’s disease (AD). While general mechanisms underlying the positive effects, including the elevated neurotrophins level, improved neurogenesis and neuroplasticity, restored angiogenesis and autophagy, and reduced neuroinflammation, have been well documented, the epigenetic mechanisms of exercise on AD, however, are still inconclusive. Exercise can regulate the expression of those AD-related genes or proteins through various epigenetic modulations, thereafter rescuing AD pathologies and improving cognitive deficits of AD. In this review, we briefly summarized recent research advances in the beneficial impacts of exercise on cognition and AD and discussed the underlying mechanisms from an epigenetic point of view, including DNA methylation, histone modifications, and non-coding RNAs. A deep understanding of how exercise epigenetically promotes cognitive and pathological recoveries in AD is crucial for the future discovery of precise exercise procedures or exercise-like remedies to treat this disease.","PeriodicalId":93251,"journal":{"name":"Ageing and neurodegenerative diseases","volume":"37 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88217675","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}
Yun Fan, Wanbing Zhao, Y. Ni, Yiqi Liu, Yilin Tang, Yimin Sun, Feng-tao Liu, Wenbo Yu, Jianjun Wu, Jian Wang
Neurodegenerative diseases (NDs) such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) constitute a spectrum of diseases characterized by the abnormal aggregation of specific amyloid fibrillar proteins; these include β-amyloid (Aβ) and tau in the form of the extracellular Aβ plaques and neuronal neurofibrillary tangles in AD and fibrillar α-synuclein aggregation in the form of Lewy bodies and Lewy neurites in PD. Transmembrane protein 106B (TMEM106B) is a type II transmembrane lysosomal protein that participates in lysosome morphology, localization, acidification, and trafficking; t is involved in the pathogenesis of several NDs, especially frontotemporal lobular degeneration with TAR DNA-binding protein immunoreactive inclusions (FTLD-TDP). Studies from four independent research groups revealed that the luminal domain of TMEM106B (120-254aa) forms amyloid fibrils in several brain regions in patients with a series of NDs and neurologically normal older adults. Given its potentially critical roles in the pathogenesis of NDs and brain aging, this surprising finding has focused attention on TMEM106B and suggested that it is nearly as fundamental as other pathogenic amyloid proteins (e.g., Aβ, tau, α-syn); nevertheless, new questions surrounding TMEM106B must be asked. In this review,we firstly introduce the physiological function of TMEM106B and its involvement in NDs. Then, we elucidate the identification and cryo-electronic microscopic structure of TMEM106B fibrils and analyze the factors that contribute to the polymorphism of TMEM106B fibrils. Finally, the potential pathogenic role of TMEM106B fibrils is discussed, and the future directions for TMEM106 research in NDs are briefly summarized.
{"title":"Newly identified transmembrane protein 106B amyloid fibrils in the human brain: pathogens or by-products?","authors":"Yun Fan, Wanbing Zhao, Y. Ni, Yiqi Liu, Yilin Tang, Yimin Sun, Feng-tao Liu, Wenbo Yu, Jianjun Wu, Jian Wang","doi":"10.20517/and.2022.30","DOIUrl":"https://doi.org/10.20517/and.2022.30","url":null,"abstract":"Neurodegenerative diseases (NDs) such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) constitute a spectrum of diseases characterized by the abnormal aggregation of specific amyloid fibrillar proteins; these include β-amyloid (Aβ) and tau in the form of the extracellular Aβ plaques and neuronal neurofibrillary tangles in AD and fibrillar α-synuclein aggregation in the form of Lewy bodies and Lewy neurites in PD. Transmembrane protein 106B (TMEM106B) is a type II transmembrane lysosomal protein that participates in lysosome morphology, localization, acidification, and trafficking; t is involved in the pathogenesis of several NDs, especially frontotemporal lobular degeneration with TAR DNA-binding protein immunoreactive inclusions (FTLD-TDP). Studies from four independent research groups revealed that the luminal domain of TMEM106B (120-254aa) forms amyloid fibrils in several brain regions in patients with a series of NDs and neurologically normal older adults. Given its potentially critical roles in the pathogenesis of NDs and brain aging, this surprising finding has focused attention on TMEM106B and suggested that it is nearly as fundamental as other pathogenic amyloid proteins (e.g., Aβ, tau, α-syn); nevertheless, new questions surrounding TMEM106B must be asked. In this review,we firstly introduce the physiological function of TMEM106B and its involvement in NDs. Then, we elucidate the identification and cryo-electronic microscopic structure of TMEM106B fibrils and analyze the factors that contribute to the polymorphism of TMEM106B fibrils. Finally, the potential pathogenic role of TMEM106B fibrils is discussed, and the future directions for TMEM106 research in NDs are briefly summarized.","PeriodicalId":93251,"journal":{"name":"Ageing and neurodegenerative diseases","volume":"167 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74218973","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}
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}
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