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 a common neurodegenerative disease,characterized clinically by both motor and non-motor symptoms.Pathologically,PD is hallmarked by the loss of dopaminergic neurons in the substantia nigra(S...Parkinson’s disease(PD)is a common neurodegenerative disease,characterized clinically by both motor and non-motor symptoms.Pathologically,PD is hallmarked by the loss of dopaminergic neurons in the substantia nigra(SN)and the formation ofα-synuclein(α-syn)containing inclusion bodies(Lewy pathology)in the surviving neurons.Diagnosis of PD is still based on clinical features.However,owing to the complexity,heterogeneity,and overlapping of its symptoms with other Parkinsonian disorders,correct diagnosis of PD remains a challenge,especially in the early stages.Therefore,there is an urgent need for biomarkers that can help correctly diagnose PD,differentiate PD from other Parkinsonian disorders,monitor the progression of the disease,and evaluate the therapeutic efficacy.Various molecules have been investigated for their utility in diagnosing PD,among whichα-syn is the most extensively investigated one due to its close implication in the etiology and pathogenesis of PD and related diseases.During the past decade,various species ofα-syn,including total,oligomeric,and phosphorylatedα-syn in various tissues,have been investigated for their utility as a potential biomarker for PD diagnosis and differential diagnosis.Various forms ofα-syn in body fluids,including cerebrospinal fluid(CSF),blood plasma,and saliva,are among the ones that are extensively investigated,since the body fluids are relatively accessible compared to the peripheral tissues.The aim of this review is to summarize the progress of studies on the utility ofα-syn in body fluid as a biomarker for PD diagnosis and differential diagnosis.展开更多
Parkinson’s disease (PD) is the second most common neurodegenerative disease. Its most prominent pathological features are the loss of dopaminergic neurons in the substantia nigra pars compacta and the deposition of ...Parkinson’s disease (PD) is the second most common neurodegenerative disease. Its most prominent pathological features are the loss of dopaminergic neurons in the substantia nigra pars compacta and the deposition of intraneuronal inclusions named Lewy bodies. Currently, the pathophysiological mechanisms of PD are not fully understood. Growing evidence suggests that insulin resistance, diabetes and PD share similar pathological processes. This raises the possibility that defective insulin signaling pathways contribute to the occurrence and development of PD. In this article, we firstly reviewed the evidence of insulin resistance from epidemiology, PD patients and animal models. We also explained the insulin signal pathways in central nervous system. We then showed the evidence that insulin resistance participates in the pathogenesis of PD via protein aggregation, mitochondrial dysfunction, neural inflammation and cognitive impairment. Finally, we introduced four categories of drugs that facilitate insulin signaling and their effects on neurodegeneration in PD.展开更多
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.
文摘Parkinson’s disease(PD)is a common neurodegenerative disease,characterized clinically by both motor and non-motor symptoms.Pathologically,PD is hallmarked by the loss of dopaminergic neurons in the substantia nigra(SN)and the formation ofα-synuclein(α-syn)containing inclusion bodies(Lewy pathology)in the surviving neurons.Diagnosis of PD is still based on clinical features.However,owing to the complexity,heterogeneity,and overlapping of its symptoms with other Parkinsonian disorders,correct diagnosis of PD remains a challenge,especially in the early stages.Therefore,there is an urgent need for biomarkers that can help correctly diagnose PD,differentiate PD from other Parkinsonian disorders,monitor the progression of the disease,and evaluate the therapeutic efficacy.Various molecules have been investigated for their utility in diagnosing PD,among whichα-syn is the most extensively investigated one due to its close implication in the etiology and pathogenesis of PD and related diseases.During the past decade,various species ofα-syn,including total,oligomeric,and phosphorylatedα-syn in various tissues,have been investigated for their utility as a potential biomarker for PD diagnosis and differential diagnosis.Various forms ofα-syn in body fluids,including cerebrospinal fluid(CSF),blood plasma,and saliva,are among the ones that are extensively investigated,since the body fluids are relatively accessible compared to the peripheral tissues.The aim of this review is to summarize the progress of studies on the utility ofα-syn in body fluid as a biomarker for PD diagnosis and differential diagnosis.
基金grants of the National Key R&D Program of China (2016YFC1306000)National Natural Science Foundation of China (81870994).
文摘Parkinson’s disease (PD) is the second most common neurodegenerative disease. Its most prominent pathological features are the loss of dopaminergic neurons in the substantia nigra pars compacta and the deposition of intraneuronal inclusions named Lewy bodies. Currently, the pathophysiological mechanisms of PD are not fully understood. Growing evidence suggests that insulin resistance, diabetes and PD share similar pathological processes. This raises the possibility that defective insulin signaling pathways contribute to the occurrence and development of PD. In this article, we firstly reviewed the evidence of insulin resistance from epidemiology, PD patients and animal models. We also explained the insulin signal pathways in central nervous system. We then showed the evidence that insulin resistance participates in the pathogenesis of PD via protein aggregation, mitochondrial dysfunction, neural inflammation and cognitive impairment. Finally, we introduced four categories of drugs that facilitate insulin signaling and their effects on neurodegeneration in PD.
