The number and health burden of Parkinson’s disease increase rapidly in China.It is estimated that China will have nearly half of the Parkinson’s disease population in the world in 2030.In this review,we present an ...The number and health burden of Parkinson’s disease increase rapidly in China.It is estimated that China will have nearly half of the Parkinson’s disease population in the world in 2030.In this review,we present an overview of epidemiology and health economics status of Parkinson’s disease across China and discuss the risk factors of Parkinson’s disease and related complications.From the view of clinical research,we also discuss the current status of clinical trials,diagnostic biomarkers,treatment of Parkinson’s disease,tertiary network and post-occupation education in Chinese Parkinson’s disease clinics.展开更多
As a multi-factorial degenerative disease, Parkinson＇s disease （PD） leads to tremor, gait rigidity, and hypokinesia, thus hampering normal living. As this disease is usually detected in the later stages when neuron...As a multi-factorial degenerative disease, Parkinson＇s disease （PD） leads to tremor, gait rigidity, and hypokinesia, thus hampering normal living. As this disease is usually detected in the later stages when neurons have degenerated completely, cure is on hold, ultimately leading to death due to the lack of early diagnostic techniques. Thus, biomarkers are required to detect the disease in the early stages when prevention is possible. Various biomarkers providing early diagnosis of the disease include those of imaging, cerebrospinal fluid, oxidative stress, neuroprotection, and inflammation. Also, biomarkers, alone or in combination, are used in the diagnosis and evolution of PD. This review encompasses various biomarkers available for PD and discusses recent advances in their development.展开更多
Background Uric acid （UA） is suspected to play a neuro-protective role in Parkinson＇s disease （PD）.This study aimed to evaluate whether the serum UA level was associated with the disease progression of PD in a re...Background Uric acid （UA） is suspected to play a neuro-protective role in Parkinson＇s disease （PD）.This study aimed to evaluate whether the serum UA level was associated with the disease progression of PD in a relatively large population of Chinese patients.Methods Serum UA levels were measured from 411 Chinese PD patients and 396 age-matched controls; following the uric acid colorimetric method,the serum creatinine （Scr） levels were also measured to reduce the bias caused by possible differences in renal excretion function.The disease progression was scored by Hoehn and Yahr （H＆Y） scales and disease durations; PD group was divided into 3 subgroups according to H＆Y scales.Independent-samples ttest was performed to analyze the differences between PD group and control group.Multiple analysis of covariance was performed to analyze the differences between PD subgroups.Spearman rank-correlation was performed to evaluate the associations between serum UA or Scr level and disease progression.Results PD patients were found to have significantly lower levels of serum UA than controls （（243.38±78.91） vs.（282.97±90.80） pmol/L,P〈0.01）.As the disease progression,the serum UA levels were gradually reduced.There was a significantly inverse correlation of UA levels with H＆Y scales （Rs=-0.429,P 〈0.01） and disease duration （Rs=-0.284,P 〈0.01） in PD patients of both females and males.No significant difference of the Scr level between PD patients and controls was found （（70.01±14.70） vs.（69.84±16.46） μmol/L）,and the Scr level was not involved in disease progression.Conclusion Lower serum UA levels may possess a higher risk of PD,which may be a potential useful biomarker to indicate the progression of PD.展开更多
Objective To evaluate the human neuroblastoma SH-SY5Y cell line as an in vitro model of dopaminergic （DAergic） neurons for Parkinson＇s disease （PD） research and to determine the effect of differentiation on this ...Objective To evaluate the human neuroblastoma SH-SY5Y cell line as an in vitro model of dopaminergic （DAergic） neurons for Parkinson＇s disease （PD） research and to determine the effect of differentiation on this cell model. Date sources The data of this review were selected from the original reports and reviews related to SH-SY5Y cells published in Chinese and foreign journals （Pubmed 1973 to 2009）. Study selection After searching the literature, 60 articles were selected to address this review. Results The SH-SY5Y cell line has become a popular cell model for PD research because this cell line posses many characteristics of DAergic neurons. For example, these cells express tyrosine hydroxylase and dopamine-13-hydroxylase, as well as the dopamine transporter. Moreover, this cell line can be differentiated into a functionally mature neuronal phenotype in the presence of various agents. Upon differentiation, SH-SY5Y cells stop proliferating and a constant cell number is subsequently maintained. However, different differentiating agents induce different neuronal phenotypes and biochemical changes. For example, retinoic acid induces differentiation toward a cholinergic neuronal phenotype and increases the susceptibility of SH-SY5Y cells to neurotoxins and neuroprotective agents, whereas treatment with retinoic acid followed by phorbol ester 12-O-tetradecanoylphorbol-13-acetate results in a DAergic neuronal phenotype and decreases the susceptibility of cells to neurotoxins and neuroprotective agents. Some differentiating agents also alter kinetics of 1-methyl-4-phenyl-pyridinium （MPP~） uptake, making SH-SY5Y cells more similar to primary mesencephalic neurons. Conclusions Differentiated and undifferentiated SH-SY5Y cells have been widely used as a cell model of DAergic neurons for PD research. Some differentiating agents afford SH-SY5Y cells with more potential for studying neurotoxiclty and neuroprotection and are thus more relevant to experimental PD research.展开更多
Neurodegenerative disorders,including Alzheimer's disease(AD) and Parkinson's disease(PD),are common disorders of the central nervous system among aging populations.In the last 10 years insights concerning the...Neurodegenerative disorders,including Alzheimer's disease(AD) and Parkinson's disease(PD),are common disorders of the central nervous system among aging populations.In the last 10 years insights concerning the etiology,diagnosis and pathogenesis of these diseases have come from research carried out by Chinese neuroscientists.Their findings include the description of Chinese patients with autosomal recessive early-onset PD,the function of the tau protein,molecular mechanisms underlying protein aggregation,and the identification of biomarkers for AD diagnosis and molecules/compounds with potential neuroprotective activities.展开更多
INTRODUCTION Sleep disturbance is one of the most common nonmotor symptoms in Parkinson's disease (PD).Sleep disturbance affects 40-98% of PD patients in the world. In China, the prevalence of PD patients with sle...INTRODUCTION Sleep disturbance is one of the most common nonmotor symptoms in Parkinson's disease (PD).Sleep disturbance affects 40-98% of PD patients in the world. In China, the prevalence of PD patients with sleep disturbance ranges from 47.66% to 89.10%. Sleep disturbance usually has adverse impact on the quality of life of PD patients. Apossible pathogenesis of PD with sleep disturbance include thalamocortical pathway degeneration and changes of neurotransmitter systems. The etiology of sleep disturbance is multifactorial,involving degeneration of areas regulating sleep,sleep structure affected by drugs,sleep disturbance induced by drug,and sleep fragmentation by multiple factors.展开更多
Gradual degeneration and loss of dopaminergic neurons in the substantia nigra,pars compacta and subsequent reduction of dopamine levels in striatum are associated with motor deficits that characterize Parkinson’s dis...Gradual degeneration and loss of dopaminergic neurons in the substantia nigra,pars compacta and subsequent reduction of dopamine levels in striatum are associated with motor deficits that characterize Parkinson’s disease(PD).In addition,half of the PD patients also exhibit frontostriatal-mediated executive dysfunction,including deficits in attention,short-term working memory,speed of mental processing,and impulsivity.The most commonly used treatments for PD are only partially or transiently effective and are available or applicable to a minority of patients.Because,these therapies neither restore the lost or degenerated dopaminergic neurons,nor prevent or delay the disease progression,the need for more effective therapeutics is critical.In this review,we provide a comprehensive overview of the current understanding of the molecular signaling pathways involved in PD,particularly within the context of how genetic and environmental factors contribute to the initiation and progression of this disease.The involvement of molecular chaperones,autophagy-lysosomal pathways,and proteasome systems in PD are also highlighted.In addition,emerging therapies,including pharmacological manipulations,surgical procedures,stem cell transplantation,gene therapy,as well as complementary,supportive and rehabilitation therapies to prevent or delay the progression of this complex disease are reviewed.展开更多
Parkinson’s disease(PD),the second most common age-associated neurodegenerative disorder,is characterized by the loss of dopaminergic(DA)neurons and the presence ofα-synuclein-containing aggregates in the substantia...Parkinson’s disease(PD),the second most common age-associated neurodegenerative disorder,is characterized by the loss of dopaminergic(DA)neurons and the presence ofα-synuclein-containing aggregates in the substantia nigra pars compacta(SNpc).Chronic neuroinflammation is one of the hallmarks of PD pathophysiology.Postmortem analyses of human PD patients and experimental animal studies indicate that activation of glial cells and increases in pro-inflammatory factor levels are common features of the PD brain.Chronic release of proinflammatory cytokines by activated astrocytes and microglia leads to the exacerbation of DA neuron degeneration in the SNpc.Besides,peripheral immune system is also implicated in the pathogenesis of PD.Infiltration and accumulation of immune cells from the periphery are detected in and around the affected brain regions of PD patients.Moreover,inflammatory processes have been suggested as promising interventional targets for PD and even other neurodegenerative diseases.A better understanding of the role of inflammation in PD will provide new insights into the pathological processes and help to establish effective therapeutic strategies.In this review,we will summarize recent progresses in the neuroimmune aspects of PD and highlight the potential therapeutic interventions targeting neuroinflammation.展开更多
Mitophagy is activated by a number of stimuli, including hypoxia, energy stress, and increased oxidative phosphorylation activity. Mitophagy is associated with oxidative stress conditions and central neurodegenerative...Mitophagy is activated by a number of stimuli, including hypoxia, energy stress, and increased oxidative phosphorylation activity. Mitophagy is associated with oxidative stress conditions and central neurodegenerative diseases. Proper regulation of mitophagy is crucial for maintaining homeostasis; conversely, inadequate removal of mitochondria through mitophagy leads to the generation of oxidative species, including reactive oxygen species and reactive nitrogen species, resulting in various neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. These diseases are most prevalent in older adults whose bodies fail to maintain proper mitophagic functions to combat oxidative species. As mitophagy is essential for normal body function, by targeting mitophagic pathways we can improve these disease conditions. The search for effective remedies to treat these disease conditions is an ongoing process, which is why more studies are needed. Additionally, more relevant studies could help establish therapeutic conditions, which are currently in high demand. In this review, we discuss how mitophagy plays a significant role in homeostasis and how its dysregulation causes neurodegeneration. We also discuss how combating oxidative species and targeting mitophagy can help treat these neurodegenerative diseases.展开更多
Early involvement of gut is observed in Parkinson’s disease (PD) and symptoms such as constipation may precede motor symptoms. α-Synuclein pathology is extensively evident in the gut and appear...Early involvement of gut is observed in Parkinson’s disease (PD) and symptoms such as constipation may precede motor symptoms. α-Synuclein pathology is extensively evident in the gut and appears to follow a rostrocaudal gradient. The gut may act as the starting point of PD pathology with spread toward the central nervous system. This spread of the synuclein pathology raises the possibility of prion-like propagation in PD pathogenesis. Recently, the role of gut microbiota in PD pathogenesis has received attention and some phenotypic correlation has also been shown. The extensive involvement of the gut in PD even in its early stages has led to the evaluation of enteric α-synuclein as a possible biomarker of early PD. The clinical manifestations of gastrointestinal dysfunction in PD include malnutrition, oral and dental disorders, sialorrhea, dysphagia, gastroparesis, constipation, and defecatory dysfunction. These conditions are quite distressing for the patients and require relevant investigations and adequate management. Treatment usually involves both pharmacological and non-pharmacological measures. One important aspect of gut dysfunction is its contribution to the clinical fluctuations in PD. Dysphagia and gastroparesis lead to inadequate absorption of oral anti-PD medications. These lead to response fluctuations, particularly delayed-on and no-on, and there is significant relationship between levodopa pharmacokinetics and gastric emptying in patients with PD. Therefore, in such cases, alternative routes of administration or drug delivery systems may be required.展开更多
Olfactory dysfunction is common in Parkinson＇s disease （PD） and often predates the diagnosis by years, reflecting early deposition of Lewy pathology, the histo- logic hallmark of PD, in the olfactory bulb. Clinical...Olfactory dysfunction is common in Parkinson＇s disease （PD） and often predates the diagnosis by years, reflecting early deposition of Lewy pathology, the histo- logic hallmark of PD, in the olfactory bulb. Clinical tests are available that allow for the rapid characterization of olfactory dysfunction, including tests of odor identification, discrimination, detection, and recognition thresholds, memory, and tests assessing the build-up of odor intensity across increasing suprathreshold stimulus concentrations. The high prevalence of olfactory impairment, along with the ease and low cost of assessment, has fostered great interest in olfaction as a potential biomarker for PD. Hyposmia may help differentiate PD from other causes of parkinsonism, and may also aid in the identification of ＂pre-motor＂ PD due to the early pathologic involvement of olfactory pathways. Olfactory function is also correlated with other non-motor features of PD and may serve as a predictor of cognitive decline. In this article, we summarize the existing literature on olfaction in PD, focusing on the potential for olfaction as a biomarker for early or differential diagnosis and prognosis.展开更多
Background:Abnormal aggregation of brainα-synuclein is a central step in the pathogenesis of Parkinson’s disease(PD),thus,it is reliable to promote the clearance ofα-synuclein to prevent and treat PD.Recent studies...Background:Abnormal aggregation of brainα-synuclein is a central step in the pathogenesis of Parkinson’s disease(PD),thus,it is reliable to promote the clearance ofα-synuclein to prevent and treat PD.Recent studies have revealed an essential role of glymphatic system and meningeal lymphatic vessels in the clearance of brain macromolecules,however,their pathophysiological aspects remain elusive.Method:Meningeal lymphatic drainage of 18-week-old A53T mice was blocked via ligating the deep cervical lymph nodes.Six weeks later,glymphatic functions and PD-like phenotypes were systemically analyzed.Results:Glymphatic influx of cerebrospinal fluid tracer was reduced in A53T mice,accompanied with perivascular aggregation ofα-synuclein and impaired polarization of aquaporin 4 expression in substantia nigra.Cervical lymphatic ligation aggravated glymphatic dysfunction of A53T mice,causing more severe accumulation ofα-synuclein,glial activation,inflammation,dopaminergic neuronal loss and motor deficits.Conclusion:The results suggest that brain lymphatic clearance dysfunction may be an aggravating factor in PD pathology.展开更多
基金This work was supported by grants from the National Natural Science Foundation of China[grant numbers 81430022,91332107,81371407].
文摘The number and health burden of Parkinson’s disease increase rapidly in China.It is estimated that China will have nearly half of the Parkinson’s disease population in the world in 2030.In this review,we present an overview of epidemiology and health economics status of Parkinson’s disease across China and discuss the risk factors of Parkinson’s disease and related complications.From the view of clinical research,we also discuss the current status of clinical trials,diagnostic biomarkers,treatment of Parkinson’s disease,tertiary network and post-occupation education in Chinese Parkinson’s disease clinics.
文摘As a multi-factorial degenerative disease, Parkinson＇s disease （PD） leads to tremor, gait rigidity, and hypokinesia, thus hampering normal living. As this disease is usually detected in the later stages when neurons have degenerated completely, cure is on hold, ultimately leading to death due to the lack of early diagnostic techniques. Thus, biomarkers are required to detect the disease in the early stages when prevention is possible. Various biomarkers providing early diagnosis of the disease include those of imaging, cerebrospinal fluid, oxidative stress, neuroprotection, and inflammation. Also, biomarkers, alone or in combination, are used in the diagnosis and evolution of PD. This review encompasses various biomarkers available for PD and discusses recent advances in their development.
基金This work was supported by grants from the National High Technology Research and Development Program of China （No.2007AA022460）,the State Key Development Program for Basic Research of China （No.2011CB510000）,and the National Natural Science Foundation of China （No.81071032）.
文摘Background Uric acid （UA） is suspected to play a neuro-protective role in Parkinson＇s disease （PD）.This study aimed to evaluate whether the serum UA level was associated with the disease progression of PD in a relatively large population of Chinese patients.Methods Serum UA levels were measured from 411 Chinese PD patients and 396 age-matched controls; following the uric acid colorimetric method,the serum creatinine （Scr） levels were also measured to reduce the bias caused by possible differences in renal excretion function.The disease progression was scored by Hoehn and Yahr （H＆Y） scales and disease durations; PD group was divided into 3 subgroups according to H＆Y scales.Independent-samples ttest was performed to analyze the differences between PD group and control group.Multiple analysis of covariance was performed to analyze the differences between PD subgroups.Spearman rank-correlation was performed to evaluate the associations between serum UA or Scr level and disease progression.Results PD patients were found to have significantly lower levels of serum UA than controls （（243.38±78.91） vs.（282.97±90.80） pmol/L,P〈0.01）.As the disease progression,the serum UA levels were gradually reduced.There was a significantly inverse correlation of UA levels with H＆Y scales （Rs=-0.429,P 〈0.01） and disease duration （Rs=-0.284,P 〈0.01） in PD patients of both females and males.No significant difference of the Scr level between PD patients and controls was found （（70.01±14.70） vs.（69.84±16.46） μmol/L）,and the Scr level was not involved in disease progression.Conclusion Lower serum UA levels may possess a higher risk of PD,which may be a potential useful biomarker to indicate the progression of PD.
文摘Objective To evaluate the human neuroblastoma SH-SY5Y cell line as an in vitro model of dopaminergic （DAergic） neurons for Parkinson＇s disease （PD） research and to determine the effect of differentiation on this cell model. Date sources The data of this review were selected from the original reports and reviews related to SH-SY5Y cells published in Chinese and foreign journals （Pubmed 1973 to 2009）. Study selection After searching the literature, 60 articles were selected to address this review. Results The SH-SY5Y cell line has become a popular cell model for PD research because this cell line posses many characteristics of DAergic neurons. For example, these cells express tyrosine hydroxylase and dopamine-13-hydroxylase, as well as the dopamine transporter. Moreover, this cell line can be differentiated into a functionally mature neuronal phenotype in the presence of various agents. Upon differentiation, SH-SY5Y cells stop proliferating and a constant cell number is subsequently maintained. However, different differentiating agents induce different neuronal phenotypes and biochemical changes. For example, retinoic acid induces differentiation toward a cholinergic neuronal phenotype and increases the susceptibility of SH-SY5Y cells to neurotoxins and neuroprotective agents, whereas treatment with retinoic acid followed by phorbol ester 12-O-tetradecanoylphorbol-13-acetate results in a DAergic neuronal phenotype and decreases the susceptibility of cells to neurotoxins and neuroprotective agents. Some differentiating agents also alter kinetics of 1-methyl-4-phenyl-pyridinium （MPP~） uptake, making SH-SY5Y cells more similar to primary mesencephalic neurons. Conclusions Differentiated and undifferentiated SH-SY5Y cells have been widely used as a cell model of DAergic neurons for PD research. Some differentiating agents afford SH-SY5Y cells with more potential for studying neurotoxiclty and neuroprotection and are thus more relevant to experimental PD research.
基金supported by the National Natural Science Foundation of China (Grant No 30721004)the National Basic Research Program of China (Grant No 2006CB500704)
文摘Neurodegenerative disorders,including Alzheimer's disease(AD) and Parkinson's disease(PD),are common disorders of the central nervous system among aging populations.In the last 10 years insights concerning the etiology,diagnosis and pathogenesis of these diseases have come from research carried out by Chinese neuroscientists.Their findings include the description of Chinese patients with autosomal recessive early-onset PD,the function of the tau protein,molecular mechanisms underlying protein aggregation,and the identification of biomarkers for AD diagnosis and molecules/compounds with potential neuroprotective activities.
文摘INTRODUCTION Sleep disturbance is one of the most common nonmotor symptoms in Parkinson's disease (PD).Sleep disturbance affects 40-98% of PD patients in the world. In China, the prevalence of PD patients with sleep disturbance ranges from 47.66% to 89.10%. Sleep disturbance usually has adverse impact on the quality of life of PD patients. Apossible pathogenesis of PD with sleep disturbance include thalamocortical pathway degeneration and changes of neurotransmitter systems. The etiology of sleep disturbance is multifactorial,involving degeneration of areas regulating sleep,sleep structure affected by drugs,sleep disturbance induced by drug,and sleep fragmentation by multiple factors.
文摘Gradual degeneration and loss of dopaminergic neurons in the substantia nigra,pars compacta and subsequent reduction of dopamine levels in striatum are associated with motor deficits that characterize Parkinson’s disease(PD).In addition,half of the PD patients also exhibit frontostriatal-mediated executive dysfunction,including deficits in attention,short-term working memory,speed of mental processing,and impulsivity.The most commonly used treatments for PD are only partially or transiently effective and are available or applicable to a minority of patients.Because,these therapies neither restore the lost or degenerated dopaminergic neurons,nor prevent or delay the disease progression,the need for more effective therapeutics is critical.In this review,we provide a comprehensive overview of the current understanding of the molecular signaling pathways involved in PD,particularly within the context of how genetic and environmental factors contribute to the initiation and progression of this disease.The involvement of molecular chaperones,autophagy-lysosomal pathways,and proteasome systems in PD are also highlighted.In addition,emerging therapies,including pharmacological manipulations,surgical procedures,stem cell transplantation,gene therapy,as well as complementary,supportive and rehabilitation therapies to prevent or delay the progression of this complex disease are reviewed.
基金by grants from the National Key Basic Research Program of China(2011CB504102)Natural Science Foundation of China(31430036,31123002,31321091).
文摘Parkinson’s disease(PD),the second most common age-associated neurodegenerative disorder,is characterized by the loss of dopaminergic(DA)neurons and the presence ofα-synuclein-containing aggregates in the substantia nigra pars compacta(SNpc).Chronic neuroinflammation is one of the hallmarks of PD pathophysiology.Postmortem analyses of human PD patients and experimental animal studies indicate that activation of glial cells and increases in pro-inflammatory factor levels are common features of the PD brain.Chronic release of proinflammatory cytokines by activated astrocytes and microglia leads to the exacerbation of DA neuron degeneration in the SNpc.Besides,peripheral immune system is also implicated in the pathogenesis of PD.Infiltration and accumulation of immune cells from the periphery are detected in and around the affected brain regions of PD patients.Moreover,inflammatory processes have been suggested as promising interventional targets for PD and even other neurodegenerative diseases.A better understanding of the role of inflammation in PD will provide new insights into the pathological processes and help to establish effective therapeutic strategies.In this review,we will summarize recent progresses in the neuroimmune aspects of PD and highlight the potential therapeutic interventions targeting neuroinflammation.
基金supported by Basic Science Research Program through the National Research Foundation of Korea(NRF) funded by the Ministry of Science,ICT and Future Planning,No.2018R1C1B5029745(to HJC),2011-0030072(to YH),2018R1D1A1B07040282(to JJ),2018R1A2B6001123(to NYJ)
文摘Mitophagy is activated by a number of stimuli, including hypoxia, energy stress, and increased oxidative phosphorylation activity. Mitophagy is associated with oxidative stress conditions and central neurodegenerative diseases. Proper regulation of mitophagy is crucial for maintaining homeostasis; conversely, inadequate removal of mitochondria through mitophagy leads to the generation of oxidative species, including reactive oxygen species and reactive nitrogen species, resulting in various neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. These diseases are most prevalent in older adults whose bodies fail to maintain proper mitophagic functions to combat oxidative species. As mitophagy is essential for normal body function, by targeting mitophagic pathways we can improve these disease conditions. The search for effective remedies to treat these disease conditions is an ongoing process, which is why more studies are needed. Additionally, more relevant studies could help establish therapeutic conditions, which are currently in high demand. In this review, we discuss how mitophagy plays a significant role in homeostasis and how its dysregulation causes neurodegeneration. We also discuss how combating oxidative species and targeting mitophagy can help treat these neurodegenerative diseases.
文摘Early involvement of gut is observed in Parkinson’s disease (PD) and symptoms such as constipation may precede motor symptoms. α-Synuclein pathology is extensively evident in the gut and appears to follow a rostrocaudal gradient. The gut may act as the starting point of PD pathology with spread toward the central nervous system. This spread of the synuclein pathology raises the possibility of prion-like propagation in PD pathogenesis. Recently, the role of gut microbiota in PD pathogenesis has received attention and some phenotypic correlation has also been shown. The extensive involvement of the gut in PD even in its early stages has led to the evaluation of enteric α-synuclein as a possible biomarker of early PD. The clinical manifestations of gastrointestinal dysfunction in PD include malnutrition, oral and dental disorders, sialorrhea, dysphagia, gastroparesis, constipation, and defecatory dysfunction. These conditions are quite distressing for the patients and require relevant investigations and adequate management. Treatment usually involves both pharmacological and non-pharmacological measures. One important aspect of gut dysfunction is its contribution to the clinical fluctuations in PD. Dysphagia and gastroparesis lead to inadequate absorption of oral anti-PD medications. These lead to response fluctuations, particularly delayed-on and no-on, and there is significant relationship between levodopa pharmacokinetics and gastric emptying in patients with PD. Therefore, in such cases, alternative routes of administration or drug delivery systems may be required.
文摘Olfactory dysfunction is common in Parkinson＇s disease （PD） and often predates the diagnosis by years, reflecting early deposition of Lewy pathology, the histo- logic hallmark of PD, in the olfactory bulb. Clinical tests are available that allow for the rapid characterization of olfactory dysfunction, including tests of odor identification, discrimination, detection, and recognition thresholds, memory, and tests assessing the build-up of odor intensity across increasing suprathreshold stimulus concentrations. The high prevalence of olfactory impairment, along with the ease and low cost of assessment, has fostered great interest in olfaction as a potential biomarker for PD. Hyposmia may help differentiate PD from other causes of parkinsonism, and may also aid in the identification of ＂pre-motor＂ PD due to the early pathologic involvement of olfactory pathways. Olfactory function is also correlated with other non-motor features of PD and may serve as a predictor of cognitive decline. In this article, we summarize the existing literature on olfaction in PD, focusing on the potential for olfaction as a biomarker for early or differential diagnosis and prognosis.
基金This work was supported by grants from the National Natural Science Foundation of China(81671070 and 81473196).
文摘Background:Abnormal aggregation of brainα-synuclein is a central step in the pathogenesis of Parkinson’s disease(PD),thus,it is reliable to promote the clearance ofα-synuclein to prevent and treat PD.Recent studies have revealed an essential role of glymphatic system and meningeal lymphatic vessels in the clearance of brain macromolecules,however,their pathophysiological aspects remain elusive.Method:Meningeal lymphatic drainage of 18-week-old A53T mice was blocked via ligating the deep cervical lymph nodes.Six weeks later,glymphatic functions and PD-like phenotypes were systemically analyzed.Results:Glymphatic influx of cerebrospinal fluid tracer was reduced in A53T mice,accompanied with perivascular aggregation ofα-synuclein and impaired polarization of aquaporin 4 expression in substantia nigra.Cervical lymphatic ligation aggravated glymphatic dysfunction of A53T mice,causing more severe accumulation ofα-synuclein,glial activation,inflammation,dopaminergic neuronal loss and motor deficits.Conclusion:The results suggest that brain lymphatic clearance dysfunction may be an aggravating factor in PD pathology.
