α-Synucleinopathies,such as Parkinson’s disease(PD),dementia with Lewy bodies(DLB)and multiple system atrophy,are a class of neurodegenerative diseases exhibiting intracellular inclusions of misfoldedα-synuclein(α...α-Synucleinopathies,such as Parkinson’s disease(PD),dementia with Lewy bodies(DLB)and multiple system atrophy,are a class of neurodegenerative diseases exhibiting intracellular inclusions of misfoldedα-synuclein(αSyn),referred to as Lewy bodies or oligodendroglial cytoplasmic inclusions(Papp-Lantos bodies).Even though the specific cellular distribution of aggregatedαSyn differs in PD and DLB patients,both groups show a significant pathological overlap,raising the discussion of whether PD and DLB are the same or different diseases.Besides clinical investigation,we will focus in addition on methodologies,such as protein seeding assays(real-time quaking-induced conversion),to discriminate between different types ofα-synucleinopathies.This approach relies on the seeding conversion properties of misfoldedαSyn,supporting the hypothesis that different conformers of misfoldedαSyn may occur in different types ofα-synucleinopathies.Understanding the pathological processes influencing the disease progression and phenotype,provoked by differentαSyn conformers,will be important for a personalized medical treatment in future.展开更多
快速眼球运动睡眠期行为障碍(rapid-eye movement sleep behavior disorder,RBD)不仅是一种睡眠障碍疾病,而且与帕金森病(Parkinson’s disease,PD)、路易体痴呆(dementia with Lewy bodies,DLB)、多系统萎缩(multiple system atrophy,M...快速眼球运动睡眠期行为障碍(rapid-eye movement sleep behavior disorder,RBD)不仅是一种睡眠障碍疾病,而且与帕金森病(Parkinson’s disease,PD)、路易体痴呆(dementia with Lewy bodies,DLB)、多系统萎缩(multiple system atrophy,MSA)等α-突触核蛋白病密切相关,通常被认为是这些疾病的早期预警。研究表明,RBD可在α-突触核蛋白病症状发作前数年至数十年出现,并预测神经变性病和认知功能障碍。本文就RBD的流行病学、临床特征及疾病进展等进行综述,进一步了解RBD与α-突触核蛋白病的关系,为临床早期诊断提供帮助。展开更多
快动眼睡眠行为障碍(rapid eye movement sleep behavior disorder,RBD)是以快动眼睡眠(rapid eye movement sleep,REM)期骨骼肌失迟缓缺失引起的临床表现,它可作为单一疾病发生,也可作为α-突触核蛋白病中的先驱症状而存在,同时影响疾...快动眼睡眠行为障碍(rapid eye movement sleep behavior disorder,RBD)是以快动眼睡眠(rapid eye movement sleep,REM)期骨骼肌失迟缓缺失引起的临床表现,它可作为单一疾病发生,也可作为α-突触核蛋白病中的先驱症状而存在,同时影响疾病的进展和程度。但关于RBD的发病机制仍不清楚,随着影像学技术的发展,脑干及黑质纹状体功能在RBD中的作用日益受到关注,脑干作为睡眠管理中心在RBD发病机制中尤显重要。本文就最近几年国外的主要神经影像学进展进行综述。展开更多
Background: α-Synuclein is a small soluble protein,whose physiological function in the healthy brain is poorly understood.Intracellular inclusions of α-synuclein,referred to as Lewy bodies(LBs),are pathological hall...Background: α-Synuclein is a small soluble protein,whose physiological function in the healthy brain is poorly understood.Intracellular inclusions of α-synuclein,referred to as Lewy bodies(LBs),are pathological hallmarks ofαsynucleinopathies,such as Parkinson’s disease(PD)or dementia with Lewy bodies(DLB).Main body:Understanding of the molecular basis as well as the factors or conditions promoting α-synuclein misfolding and aggregation is an important step towards the comprehension of pathological mechanism ofαsynucleinopathies and for the development of efficient therapeutic strategies.Based on the conversion and aggregation mechanism of α-synuclein,novel diagnostic tests,such as protein misfolding seeded conversion assays,e.g.the real-time quaking-induced conversion(RT-QuIC),had been developed.In diagnostics, α-synuclein RT-QuIC exhibits a specificity between 82 and 100%while the sensitivity varies between 70 and 100%among different laboratories.In addition,the α-synuclein RT-QuIC can be used to study the α-synuclein-seeding-characteristics of different α-synucleinopathies and to differentiate between DLB and PD.Conclusion:The variable diagnostic accuracy of current α-synuclein RT-QuIC occurs due to different protocols,cohorts and material etc..An impact of micro-environmental factors on the α-synuclein aggregation and conversion process and the occurrence and detection of differential misfolded α-synuclein types or strains might underpin the clinical heterogeneity of α-synucleinopathies.展开更多
Alpha-synucleinopathies(α-synucleinopathies)are a diverse group of neurodegenerative diseases comprising Parkinson’s disease(PD),dementia with Lewy bodies(DLB),and multiple system atrophy(MSA).Although in all these ...Alpha-synucleinopathies(α-synucleinopathies)are a diverse group of neurodegenerative diseases comprising Parkinson’s disease(PD),dementia with Lewy bodies(DLB),and multiple system atrophy(MSA).Although in all these diseases there exist abnormal accumulation of alpha-synuclein(α-syn)aggregates in nerve tissues,the pathological lesions formed byα-syn aggregates and their cellular locations are quite different.In PD and DLB,the hallmark pathological lesions are Lewy bodies(LBs)and Lewy neurites(LNs),which are localized in the neuronal somata and processes.In MSA,the characteristic pathologic structures are glial cytoplasmic inclusions,which are deposited in the cytoplasm of oligodendrocytes.The fact that PD and MSA have distinct pathologicalα-syn lesions suggest that different mechanisms play a role in the pathogenesis of the two diseases.In this review article,we compare the clinical manifestations and pathological features of PD and MSA,the two common synucleinopathies,and discuss the potential mechanisms for the formation ofα-syn aggregates and their pathologic roles in PD and MSA.展开更多
Parkinson’s disease(PD)is referring to the multi-systemicα-synucleinopathy with Lewy bodies deposited in midbrain.In ageing,the environmental and genetic factors work together and overactive major histocompatibility...Parkinson’s disease(PD)is referring to the multi-systemicα-synucleinopathy with Lewy bodies deposited in midbrain.In ageing,the environmental and genetic factors work together and overactive major histocompatibility complex pathway to regulate immune reactions in central nerve system which resulting in neural degeneration,especially in dopaminergic neurons.As a series of biomarkers,the human leukocyte antigen genes with its related proteomics play cortical roles on the antigen presentation of major histocompatibility complex molecules to stimulate the differentiation of T lymphocytes and i-proteasome activities under their immune response to the PD-related environmental alteration and genetic variation.Furthermore,dopaminergic drugs change the biological characteristic of T lymphatic cells,affect theα-synuclein presentation pathway,and inhibit T lymphatic cells to release cytotoxicity in PD development.Taking together,the serum inflammatory factors and blood T cells are involved in the immune dysregulation of PD and inspected as the potential clinic biomarkers for PD prediction.展开更多
基金Open Access funding enabled and organized by Projekt DEAL.This study was funded by the Alzheimer Forschungs Initiative,project number 20026.
文摘α-Synucleinopathies,such as Parkinson’s disease(PD),dementia with Lewy bodies(DLB)and multiple system atrophy,are a class of neurodegenerative diseases exhibiting intracellular inclusions of misfoldedα-synuclein(αSyn),referred to as Lewy bodies or oligodendroglial cytoplasmic inclusions(Papp-Lantos bodies).Even though the specific cellular distribution of aggregatedαSyn differs in PD and DLB patients,both groups show a significant pathological overlap,raising the discussion of whether PD and DLB are the same or different diseases.Besides clinical investigation,we will focus in addition on methodologies,such as protein seeding assays(real-time quaking-induced conversion),to discriminate between different types ofα-synucleinopathies.This approach relies on the seeding conversion properties of misfoldedαSyn,supporting the hypothesis that different conformers of misfoldedαSyn may occur in different types ofα-synucleinopathies.Understanding the pathological processes influencing the disease progression and phenotype,provoked by differentαSyn conformers,will be important for a personalized medical treatment in future.
文摘快速眼球运动睡眠期行为障碍(rapid-eye movement sleep behavior disorder,RBD)不仅是一种睡眠障碍疾病,而且与帕金森病(Parkinson’s disease,PD)、路易体痴呆(dementia with Lewy bodies,DLB)、多系统萎缩(multiple system atrophy,MSA)等α-突触核蛋白病密切相关,通常被认为是这些疾病的早期预警。研究表明,RBD可在α-突触核蛋白病症状发作前数年至数十年出现,并预测神经变性病和认知功能障碍。本文就RBD的流行病学、临床特征及疾病进展等进行综述,进一步了解RBD与α-突触核蛋白病的关系,为临床早期诊断提供帮助。
文摘快动眼睡眠行为障碍(rapid eye movement sleep behavior disorder,RBD)是以快动眼睡眠(rapid eye movement sleep,REM)期骨骼肌失迟缓缺失引起的临床表现,它可作为单一疾病发生,也可作为α-突触核蛋白病中的先驱症状而存在,同时影响疾病的进展和程度。但关于RBD的发病机制仍不清楚,随着影像学技术的发展,脑干及黑质纹状体功能在RBD中的作用日益受到关注,脑干作为睡眠管理中心在RBD发病机制中尤显重要。本文就最近几年国外的主要神经影像学进展进行综述。
基金The project was supported by the German Academic Exchange Service(DAAD)project 57421248by the Alzheimer Forschung Initiative(AFI)project 17022the Instituto Carlos Ⅲ(Miguel Servet programme—CP16/00041)to FL.
文摘Background: α-Synuclein is a small soluble protein,whose physiological function in the healthy brain is poorly understood.Intracellular inclusions of α-synuclein,referred to as Lewy bodies(LBs),are pathological hallmarks ofαsynucleinopathies,such as Parkinson’s disease(PD)or dementia with Lewy bodies(DLB).Main body:Understanding of the molecular basis as well as the factors or conditions promoting α-synuclein misfolding and aggregation is an important step towards the comprehension of pathological mechanism ofαsynucleinopathies and for the development of efficient therapeutic strategies.Based on the conversion and aggregation mechanism of α-synuclein,novel diagnostic tests,such as protein misfolding seeded conversion assays,e.g.the real-time quaking-induced conversion(RT-QuIC),had been developed.In diagnostics, α-synuclein RT-QuIC exhibits a specificity between 82 and 100%while the sensitivity varies between 70 and 100%among different laboratories.In addition,the α-synuclein RT-QuIC can be used to study the α-synuclein-seeding-characteristics of different α-synucleinopathies and to differentiate between DLB and PD.Conclusion:The variable diagnostic accuracy of current α-synuclein RT-QuIC occurs due to different protocols,cohorts and material etc..An impact of micro-environmental factors on the α-synuclein aggregation and conversion process and the occurrence and detection of differential misfolded α-synuclein types or strains might underpin the clinical heterogeneity of α-synucleinopathies.
基金the authors are supported by grants from Natural Science Foundation of China(81671244,81371200,and 81401042)a special fund from Key Laboratory of Neurodegenerative Disease,Ministry of Education(PXM2019_026283_000002)+1 种基金Beijing Municipal Science and Technology Commission(Z161100005116011,Z171100000117013)Beijing Municipal commission of Health and Family Planning(PXM2017_026283_000002).
文摘Alpha-synucleinopathies(α-synucleinopathies)are a diverse group of neurodegenerative diseases comprising Parkinson’s disease(PD),dementia with Lewy bodies(DLB),and multiple system atrophy(MSA).Although in all these diseases there exist abnormal accumulation of alpha-synuclein(α-syn)aggregates in nerve tissues,the pathological lesions formed byα-syn aggregates and their cellular locations are quite different.In PD and DLB,the hallmark pathological lesions are Lewy bodies(LBs)and Lewy neurites(LNs),which are localized in the neuronal somata and processes.In MSA,the characteristic pathologic structures are glial cytoplasmic inclusions,which are deposited in the cytoplasm of oligodendrocytes.The fact that PD and MSA have distinct pathologicalα-syn lesions suggest that different mechanisms play a role in the pathogenesis of the two diseases.In this review article,we compare the clinical manifestations and pathological features of PD and MSA,the two common synucleinopathies,and discuss the potential mechanisms for the formation ofα-syn aggregates and their pathologic roles in PD and MSA.
基金This review was supported by research grants from the State Key Development Program for Basic Research of China(2011CB510000)the National Natural Science Foundation of China(81271428,81471292,U1503222 and 81430021)+2 种基金the keypoint Science Foundation of Guangdong of China(2015A030311021)a grant supported by technology project of Guangzhou(201604020152)a grant supported by assisting research project of science and technology for Xinjiang(201591160).
文摘Parkinson’s disease(PD)is referring to the multi-systemicα-synucleinopathy with Lewy bodies deposited in midbrain.In ageing,the environmental and genetic factors work together and overactive major histocompatibility complex pathway to regulate immune reactions in central nerve system which resulting in neural degeneration,especially in dopaminergic neurons.As a series of biomarkers,the human leukocyte antigen genes with its related proteomics play cortical roles on the antigen presentation of major histocompatibility complex molecules to stimulate the differentiation of T lymphocytes and i-proteasome activities under their immune response to the PD-related environmental alteration and genetic variation.Furthermore,dopaminergic drugs change the biological characteristic of T lymphatic cells,affect theα-synuclein presentation pathway,and inhibit T lymphatic cells to release cytotoxicity in PD development.Taking together,the serum inflammatory factors and blood T cells are involved in the immune dysregulation of PD and inspected as the potential clinic biomarkers for PD prediction.
