ABSTRACT
Parkinson′s disease (PD) is the most common age-related neurodegenerative disease, which has the effects on the patients′ quality of life and brings a huge burden to the society and family. The pathological feature of PD is the abnormal accumulation of alpha-synuclein (α-syn) in the brain of substantia nigra-striatum, mediating the death of dopaminergic neurons. However, further studies have found that α-syn mediates the abnormal function of astrocytes leading to the destruction of the blood-brain barrier and the release of inflammatory factors caused by microglia, which are related to the pathogenesis of PD. Therefore, neurons, glial cells, and blood vessels as a whole named neurovascular unit can better reflect the pathophysiological environment of PD and reveal the PD pathogenesis. Studies have detected the ways of α-syn transmission, such as prion-like, tunneling nanotubes, exosomes, are connected with the pathogenesis and progression of PD. The Braak stage and the prospective cohort of early PD provide a view that the peripheral α-syn to the central nervous system may be an another important way to mediate the pathogenesis and progression of PD. The research about the abnormal aggregation and spread of α-syn can provide the new theory for the pathogenesis of PD and the new disease modifying therapy of PD. This article reviews the role of abnormal aggregation and transmission of α-syn in the pathogenesis of PD.
ABSTRACT
Idiopathic rapid eye movement (REM) sleep behavior disorder is recognized as a prodromal stage of α-synucleinopathies such as Parkinson′s disease, Lewy body dementia and multiple system atrophy. It is important to timely identify early predictors that can predict early conversion into α-synucleinopathies. This review provided an update on classic and novel early predictors of α-synucleinopathies in patients with idiopathic REM sleep behavior disorder and provided a comprehensive understanding on the phenotypic transformation of the disease.
ABSTRACT
Parkinson′s disease is a degenerative disease, in which cognitive impairment is main non-motor symptom. It can develop to dementia and seriously affect the quality of life and life expectancy of patients. Therefore, a correct understanding of the etiology and mechanism of cognitive impairment in Parkinson′s disease is helpful for the disease diagnosis and treatment. In recent years, the correlation between vascular factors and the development of Parkinson′s disease has become a research hot topic. This article reviewed the research progress of the correlation between vascular related factors and cognitive impairment in Parkinson′s disease.
ABSTRACT
Parkinson's disease (PD) is a common neurodegenerative disease,pathogenesis of which is extremely complex.To explore the potential pathophysiological mechanism of PD and find effective treatment methods to improve symptoms,modify the disease and delay the progression are the major problems to be solved urgently.Studies have shown that transcranial magnetic stimulation (TMS) has a broad clinical application prospect,which might help clinicians to explore the pathophysiological mechanism of PD and provide new ideas for exploring new targets for diagnosis and treatment in the future.Meanwhile,TMS might play important roles in the treatment of PD motor and non-motor symptoms through enhancing synaptic plasticity,protecting monoamine neurons,increasing the monoamine neurotransmitter level in the brain,and adjusting the brain network with dysfunction.
ABSTRACT
Objective To establish an in vitro cell model of Parkinson disease with SHSY5Y cells over-expressing human A53T mutant alpha-synuclein and to examine the effects of Aβ1-42 oligomer on cell survival and autophagy function in the cell model Method The recombinant lentivirus containing the A53T mutant alpha-synuclein gene or empty vector were transfected to SHSY5Y cells. The expression of α-synuclein mRNA in SHSY5Y cells was detected by RT-qPCR. The effect of Aβ1-42 oligomer on cell proliferation was detected with CCK-8 after incubation with Aβ1-42 oligomer for 24 hours. The autophagy-related proteins were evaluated with Western Blot. Result The mRNA and protein levels of alpha-synuclein were significantly increased in SHSY5Y cells expressing alpha-synuclein. There were no significant difference in the cell proliferation between alpha-synuclein group and control group (P<0.001) . Incubation with Aβ1-42 oligomer significantly decreased the proliferation rate in alpha-synuclein group in a dose-dependent manner compared with the control group. The levels of autophagy related proteins including LC3-Ⅱ and Beclin-1 were significantly lower in alpha-synuclein group than in control group (P<0.05). Conclusion This work has constructed an in vitro cell model of Parkinson′s disease. The over-expression of A53T mutant alpha-synuclein do not affect the cell survival whereas the Aβ1-42 oligomer exhibits toxic effects on cells expressing alpha-synuclein possible through suppression of the autophagy activation.
ABSTRACT
Objective To study the relationship between level of plasma glucose and cognitive function in patients with Parkinson's disease.Methods Two hundred PD patients were assessed cognitive function using Mini-Mental State Examination (MMSE),Montreal Cognitive Assessment (MoCA),Wechsler Intelligence Scale and Wechsler Memory Scale.The patients were divided into cognitive normal group (n=91) and cognitive impairment group (n=109).One hundred twenty-six normal subjects were enrolled as control group (n=126).The levels of fasting plasma glucose (FPG),postprandial plasma glucose (2hPPG),glycosylated hemoglobin (HbAlc) and the prevalence of diabetes mellitus were compared among the groups.The effect of blood glucose level on the cognitive function of PD patients was analyzed by Binary Logistic Regression.Results The levels of FPG,HbAlc and the prevalence of diabetes mellitus [5.19 (0.72),5.7％ (0.5％),14％] were significantly higher than those in the normal control group [4.85(0.79),5.6％ (0.5％),6％] (P＜0.05).The levels of FPG in PD patients with cognitive impairment [5.21 (1.32)] was significantly higher than that in PD patients with cognitive normal group [4.81 (0.95)] (P＜0.05).Although 2hPPG and HbAlc increased slightly in PD patients with cognitive impairment,the difference did not reach an significant level (P＞0.05).Binary Logistic Regression analysis showed that FPG(OR:1.764;95％ CI:0.06-3.244;P=0.068) was not associated with the impaired cognitive function in PD patients.Conclusion The present study has not revealed an association between the incidence of cognitive impairment in patients with PD and plasma glucose level although high plasma glucose may be a high risk factor for PD patients.