Abnormal modification of alpha-synuclein and its mechanism in Parkinson's disease / 中国组织工程研究

BACKGROUND:The formation of Lewy bodies due to abnormal α-synuclein aggregation is a characteristic pathological change in Parkinson's disease.In recent years,several studies have revealed that the formation of α-synuclein aggregates is closely related to its post-translational modifications.The modification of α-synuclein such as phosphorylation,nitration,acetylation,and ubiquitination has attracted extensive attention in the pathogenesis and progression of Parkinson's disease. OBJECTIVE:To review the research progress in the effect of modification types and sites of α-synuclein on the characteristic pathological formation and progression of Parkinson's disease. METHODS:PubMed and CNKI databases were searched by the first author with the key words of"α-synuclein,Parkinson's disease,phosphorylation,acetylation,ubiquitination,nitration"in English and Chinese respectively to collect and sort out the literature related to abnormal modification of α-synuclein in recent years.Finally,61 articles were included for further review. RESULTS AND CONCLUSION:Abnormal modification of α-synuclein is closely related to its protein structure and its positive and negative charges.Its amino terminus is positively charged and prone to ubiquitination and acetylation modifications.The central hydrophobic region is prone to forming β-pleated sheet due to its hydrophobic property.The carboxyl terminus is negatively charged,which is the main phosphorylation modification region.Phosphorylation modification sites promote phosphorylation modification and are closely related to α-synuclein aggregation,while protein kinases can target the activation of translational modifications,which may help to promote or inhibit aggregate formation.The degradation pathway of α-synuclein mainly plays a role in removing pathological proteins.Various kinase catalysts contribute to impaired protein ubiquitination modifications that lead to abnormal protein accumulation,thereby exacerbating neurodegeneration.The amino-terminal acetylation of α-synuclein improves the shuttle ability of the protein to the cell membrane and slows down the protein aggregation,which may be the protection target of nerve cells.However,the acetylation modification of the mutant protein produces the opposite effect.The protein nitration modification is mainly related to oxidative stress.The aggregation tendency of the protein modified by nitration is enhanced under the action of reactive oxygen species.Different post-translational modifications have different effects.Therefore,elucidating the main mechanisms of their post-translational modifications and inhibiting the post-translational modifications that contribute to protein aggregation may provide a reference for new targets for early diagnosis and treatment of Parkinson's disease.

Effects of olfactory three needle on apolipoprotein E and pathological substrates in the hippocampus of mice with Parkinson's disease dementia / 中国康复医学杂志

Objective:To explore the mechanism of olfactory three needle therapy on Parkinson's disease dementia(PDD)by observing its effects on expression of apolipoprotein E(ApoE)、glial fibrillary acidic protein(GFAP)and related core pathology substrates in the hippocampus of PDD model mice. Method:Male C57BL/6 mice were randomly divided into four groups:control group(Control),sham opera-tion group(Sham),model group(Model)and acupuncture electrotherapy group(AE),with 10 mice in each group.The PD model was established by injecting 6-OHDA into the medial forebrain tract(MFB)and PDD mice were selected.After successful modeling and selection,the AE group received"olfactory three needle"electro acupuncture treatment.After 14 days of intervention,Morris water maze test and shuttle box test were used to evaluate the learning and memory ability of mice in each group.Hematoxylin-eosin(HE)staining was used to observe the pathological changes of hippocampal CA1 region.Western blotting was used to detect the expression of α-syn,Aβ and ApoE proteins in hippocampal CA1 region.The co-location rate of ApoE and GFAP in hippocampal CA1 region was observed by double immunofluorescence markers. Result:Compared with Model group,the AE group exhibited a shortened escape latency in water maze(P＜0.01),increased platform crossing(P＜0.05),increased active escape times of shuttle box(P＜0.05),and reduced the average total time of electric stimulation(P＜0.01).In the Model group,the neurons in the hippocampal CA1 area were sparsely arranged and showed signs of degeneration and necrosis;and cell nuclei were small,hyperchromatic and had unclear structures,indicating the appearance of nuclear pyrosis.In contrast,the AE group showed significant improvements in neuronal pathology,with most cells regularly arranged,round and large nuclei,lightly stained and clearly shaped.Compared with the Model group,the expression levels of α-syn,Aβ,ApoE protein and the co-localization rate of ApoE and GFAP in hippocampal CA1 region in AE group were decreased(P＜0.01,P＜0.01,P＜0.01,P＜0.05). Conclusion:The"Olfactory three needle"acupuncture can improve the cognitive ability and restore the morpho-logical structure and function of neurons in PDD mice.The mechanism may be related to the inhibition of ApoE expression in astrocytes and the reduction of α-syn and Aβ deposition in hippocampal CA1 region.

Roles of autophagy-mediated alpha-synuclein clearance in the development of Parkinson disease / 中华行为医学与脑科学杂志

Parkinson disease (PD) is a common chronic neurodegenerative disease that seriously affects the quality of life of patients and has become an important population health problem in society.The typical neuropathological feature of PD is the abnormal aggregation of α-synuclein (α-Syn) in the substantia nigra-striatal region, causing dopaminergic degenerative necrosis of neurons. With further research, it was found that cellular autophagy mediated the clearance process of pathological α-Syn involved in the pathogenesis of PD. Autophagy is an important pathway for cells to remove abnormal aggregated proteins and senescence-damaged organelles, and autophagic removal of abnormal α-Syn deposition can maintain cellular homeostasis and protect dopaminergic neurons. In addition, impaired autophagy causes α-Syn aggregation, increases α-Syn propagation in the brain, promotes the degeneration of dopaminergic neurons, and is involved in the development of PD.PD-related genes affect autophagy regulation, and mutations in related genes can lead to impaired lysosomal function to block autophagy. At the same time, abnormal aggregation of α-Syn further disrupts the autophagy process, reduces the autophagic clearance capacity, and increases the accumulation of neurotoxicity. Impaired autophagy and abnormal α-Syn aggregation are important mechanisms of degeneration in nigrostriatal dopaminergic neurons. Therefore, studies targeting autophagy and abnormal α-Syn aggregation may provide new ideas for the pathogenesis of PD, and reducing α-Syn accumulation by increasing autophagic flux may become a key target for the treatment of PD.

Parkinson's Disease: A Multisystem Disorder / 神经科学通报·英文版

The way sporadic Parkinson's disease (PD) is perceived has undergone drastic changes in recent decades. For a long time, PD was considered a brain disease characterized by motor disturbances; however, the identification of several risk factors and the hypothesis that PD has a gastrointestinal onset have shed additional light. Today, after recognition of prodromal non-motor symptoms and the pathological processes driving their evolution, there is a greater understanding of the involvement of other organ systems. For this reason, PD is increasingly seen as a multiorgan and multisystemic pathology that arises from the interaction of susceptible genetic factors with a challenging environment during aging-related decline.

Association of Glial Activation and α-Synuclein Pathology in Parkinson's Disease / 神经科学通报·英文版

The accumulation of pathological α-synuclein (α-syn) in the central nervous system and the progressive loss of dopaminergic neurons in the substantia nigra pars compacta are the neuropathological features of Parkinson's disease (PD). Recently, the findings of prion-like transmission of α-syn pathology have expanded our understanding of the region-specific distribution of α-syn in PD patients. Accumulating evidence suggests that α-syn aggregates are released from neurons and endocytosed by glial cells, which contributes to the clearance of α-syn. However, the activation of glial cells by α-syn species produces pro-inflammatory factors that decrease the uptake of α-syn aggregates by glial cells and promote the transmission of α-syn between neurons, which promotes the spread of α-syn pathology. In this article, we provide an overview of current knowledge on the role of glia and α-syn pathology in PD pathogenesis, highlighting the relationships between glial responses and the spread of α-syn pathology.

Research progress of GBA1 variation and Parkinson′s disease / 中华神经科杂志

GBA1 is one of the common risk genes of Parkinson′s disease (PD), which encodes glucocerebrosidase. It is difficult to distinguish PD patients with heterozygous variants of GBA1 ( GBA1-PD) from idiopathic Parkinson′s disease patients, but GBA1-PD tends to progress faster, be more severe, and be more likely to be associated with cognitive impairment and other non-motor symptoms. The pathological mechanism of the increased risk of PD in GBA1 heterozygous variant carriers may be related to autophagy-lysosome dysfunction and mitochondrial dysfunction. Targeted therapy for GBA1 is expected to become a new direction of precision therapy for PD. In this article, the epidemiology and clinical features of GBA1-PD, the possible pathogenesis of GBA1 variation, and the therapeutic strategies for GBA1-PD were elaborated.

Progress in treatment of multiple system atrophy / 临床神经病学杂志

Multiple system atrophy(MSA)is an adult-onset and progressive neurodegenerative disease,is clinically classified into two subtypes:MSA with predominant parkinsonism(MSA-P)and MSA with predominant cerebellar ataxia(MSA-C),characterized by dysautonomia and dyskinesia.The etiology of MSA is still unknown,multiple pathogenic factors are involved in the pathogenesis of this disease,therefore,in addition to limited symptomatic treatment,there is still a lack of disease modifying therapy to prevent the progress of the disease.Currently,animal and clinical studies targeting α-synuclein,neuroinflammation and neurotrophic supporting are being explored,so this article reviewed the latest progresses to improve the clinical understanding of treatment of MSA.

Blood plasma from patients with Parkinson's disease and multiple system atrophy enhances ability of α-synuclein aggregates to destroy cell membrane / 中华神经医学杂志

Objective:To explore the role of α-synuclein (α-Syn) in pathogenesis of Parkinson's disease (PD) and multiple system atrophy (MSA) by observing the ability of α-Syn aggregates incubated with PD and MSA patients' plasma to destroy cell membrane.Methods:Peripheral blood samples were collected from 5 PD patients and 5 MSA patients diagnosed in Department of Neurology, Affiliated Hospital of Guilin Medical University from January 2018 to January 2022, as well as 5 physical examination healthy control subjects (HCs) during the same period. The α-Syn was dissolved in 0.01 mol/L PBS and then incubated with PBS, and plasma from HCs, PD patients and MSA patients at 37 ℃ for 4 d, respectively (named as PBS group, HC group, PD group and MSA group). Small unilamellar vesicles (SUVs) containing calcein were prepared with acidic phospholipid, 1-palmityl-2-oleoyl-Sn-glycerol-3-phospho-L-serine (POPS), by membrane dispersion-ultrasonic method; the particle size and morphology of SUVs were analyzed by Malvern Zetasizer Nano ZS and transmission electron microscope. SUVs and human neuroblastoma cells (SH-SY5Y) were treated with different concentrations of α-Syn aggregates (0.5, 1.0, 2.0, 4.0, 8.0 and 16.0 μmol/L). The abilities of α-Syn aggregates formed under different conditions to destroy liposomes and cell membrane were evaluated by measuring the calcein relative release and intracellular calcein fluorescent value after dialysis.Results:(1) Destructive effect of α-Syn aggregates on SUVs: calcein induced by α-Syn aggregates in each group increasingly released with the increase of protein concentration; at protein concentration of 8 μmol/L, the calcein released from SUVs in PD and MSA groups was significantly higher than that in PBS and HC groups, and the calcein released from SUVs in MSA group was further significantly higher than that in the PD group ( P<0.05). (2) Destructive effect of α-Syn aggregates on cell membrane in SH-SY5Y: the calcein fluorescent value in each group decreased with the increase of protein concentration; at protein concentration of 8 μmol/L, the intracellular calcein fluorescent value in PD and MSA groups were significantly decreased compared with that in PBS and HC groups ( P<0.05); the intracellular calcein fluorescent value in MSA group was further significantly decreased compared with that in PD group ( P<0.05). (3) Effect of α-Syn aggregates on SH-SY5Y cell survival: at protein concentration of 8 μmol/L, the viability of SH-SY5Y cells in each group decreased obviously; PD and MSA groups had significantly decreased cell viability compared with PBS and HC groups ( P<0.05); and the viability in MSA group was further statistically decreased compared with that in PD group ( P<0.05). Conclusion:The ability of α-Syn aggregates incubated with PD and MSA patients' plasma to destroy cell membrane is greater than that with HCs' plasma, especially those with MSA patients' plasma.

Recent advance in role of real-time quaking-induced conversion technique in α-synucleinopathies / 中华神经医学杂志

Lewy bodies formed by abnormal deposition of α-synuclein (α-syn) in neurons and glial cells are diagnostic markers of α-synucleinopathies. However, the early diagnosis of α-synucleinopathies is delayed due to the difficulty of brain biopsy at present. Because that α-syn can produce prion-like replication and spread to the periphery under pathological conditions, the ultramicro detection of pathologic α-syn in extracranial tissues by real-time quaking-induced conversion (RT-QuIC) technique can provide a basis for early diagnosis of α-synucleinopathies. In this paper, we review RT-QuIC technique in detecting α-syn seeding activity in different tissues of patients with α-synucleinopathies to summarize the potential value of RT-QuIC technique in early diagnosis or differential diagnosis of α-synucleinopathies.

Recent progress of epigallocatechin 3-gallate for treatment of Parkinson's disease / 中国药理学通报

Epigallocatechin 3-gallate (EGCG) is an abundant polyphenolie component originating from green tea extract that has exhibited versatile bioactivities in combating several diseases. During the last decade, EGCG are effective in experimental models of Parkinson's disease (PD). Several experimental studies suggest the pleiotropic neuroprotective effects, aiding to EGCG as an appealing therapeutic strategy in PD. Therefore, in this review we focus on the effects of EGCG on anti-apoptosis, anti-oxidant, anti-inflammation, modulation of dopamine production, and the aggregation of a-synuclein. We aim to compile the recent updates and cellular and molecular mechanisms of neuroprotection of EGCG in PD. This review highlights the pharmacological features of EGCG and its therapeutic implications in PD.

Corynoxine B targets at HMGB1/2 to enhance autophagy for α-synuclein clearance in fly and rodent models of Parkinson's disease

Parkinson's disease (PD) is the most common neurodegenerative movement disease. It is featured by abnormal alpha-synuclein (α-syn) aggregation in dopaminergic neurons in the substantia nigra. Macroautophagy (autophagy) is an evolutionarily conserved cellular process for degradation of cellular contents, including protein aggregates, to maintain cellular homeostasis. Corynoxine B (Cory B), a natural alkaloid isolated from Uncaria rhynchophylla (Miq.) Jacks., has been reported to promote the clearance of α-syn in cell models by inducing autophagy. However, the molecular mechanism by which Cory B induces autophagy is not known, and the α-syn-lowering activity of Cory B has not been verified in animal models. Here, we report that Cory B enhanced the activity of Beclin 1/VPS34 complex and increased autophagy by promoting the interaction between Beclin 1 and HMGB1/2. Depletion of HMGB1/2 impaired Cory B-induced autophagy. We showed for the first time that, similar to HMGB1, HMGB2 is also required for autophagy and depletion of HMGB2 decreased autophagy levels and phosphatidylinositol 3-kinase III activity both under basal and stimulated conditions. By applying cellular thermal shift assay, surface plasmon resonance, and molecular docking, we confirmed that Cory B directly binds to HMGB1/2 near the C106 site. Furthermore, in vivo studies with a wild-type α-syn transgenic drosophila model of PD and an A53T α-syn transgenic mouse model of PD, Cory B enhanced autophagy, promoted α-syn clearance and improved behavioral abnormalities. Taken together, the results of this study reveal that Cory B enhances phosphatidylinositol 3-kinase III activity/autophagy by binding to HMGB1/2 and that this enhancement is neuroprotective against PD.

Research progress of α-synuclein in the pathogenesis of Parkinson's disease / 局解手术学杂志

Parkinson's disease(PD)is the most common neurodegenerative disease,and Lewy bodies(LBs)is the most typical pathological change.α-synuclein(α-syn),as the main component of LBs,is considered as the pathogenic factor of PD.According to the transmission hypothesis,pathological α-syn can be transported from damaged neurons to normal neurons,leading to pathological misfolding and aggregation of α-syn in recipient neurons,resulting in cascading neuronal damage.According to the hypothesis of gut-brain axis,pathological α-syn can be produced in the intestine,and uploaded to the central nervous system via the vagus nerve.In this paper,the role of α-syn in the pathogenesis of PD is summarized,in order to provide reference for the study of intervention targets of PD.

Advances in NLRP3-mediated neuroinflammation in Parkinson disease / 中华行为医学与脑科学杂志

Parkinson disease (PD) is a neurodegenerative disorder characterized by striatal dopamine deficiency due to degenerative death of midbrain nigrostriatal dopaminergic neurons and the presence of intracellular α-synuclein aggregates.The inflammation caused by NLRP3 inflammasome mediated by microglia overactivation in the midbrain substantia nigra promotes the degeneration of dopamine neurons and plays a key role in the development of PD.α-synuclein aggregation, mitochondrial dysfunction, autophagy and dopamine receptor defects are key regulators of the degeneration of substantia nigra neurons mediated by microglia NLRP3 inflammasome activation.In this paper, we summarize the role of molecular mechanisms of microglia NLRP3 inflammasome activation and regulation in PD, and discuss the main potential PD therapeutic targets or approaches targeting NLRP3 inflammasome mechanisms, with the aim of providing the theoretical basis and insight for PD treatment.

Regulating mechanism of dynein heavy chain on autophagic degradation of α-synuclein in Parkinson disease model cells / 中华行为医学与脑科学杂志

Objective:To explore the regulatory mechanism of α-synuclein in the degradation of autophagy-lysosome pathway(ALP) in Parkinson disease(PD) model cells after interference or overexpression of dynein heavy chain(Dynhc) gene.Methods:SH-SY5Y cells were divided into control group, PD group, Dynhc interference group, Dynhc overexpression group, and Dynhc interference+ rapamycin group according to experimental requirements.Using Western blot to detect Dynhc, α-synuclein, microtubule-associated protein l light chain 3 (LC3), lysosome-associated membrane protein 2 (LAMP2), tubulin, dynein activator protein p150, and kinesin KIF5B.Flow cytometry was used to detect the level of cell apoptosis.Immunoconfocal microscopy was used to observe the structure of tubulin and the co-localization of LC3 and LAMP.SPSS 23.0 software was used for statistical analysis.One-way ANOVA was used for inter group comparisons, and further pairwise comparisons were conducted by LSD- t test. Results:There were statistically significant differences in the expression of α-synuclein, autophagy-related proteins, microtubules, and microtubule-related proteins among cells in the 5 groups(all P<0.001). The protein expression levels of Dynhc, α-synuclein, LC3, LAMP2, p150, and KIF5B in the PD group were higher than those in the control group (all P<0.05). The protein levels of Dynhc, LAMP2, tubulin and p150 in the Dynhc interference group were lower than those in the PD group (all P<0.05), while the protein levels of α-synuclein, LC3 and KIF5B were higher than those in the PD group (all P<0.05). The protein levels of α-synuclein, LC3, and KIF5B in the Dynhc overexpression group were lower than those in the PD group (all P<0.05), while the protein levels of Dynhc, LAMP2 and p150 were higher than those in the PD group (all P<0.05). The protein level of LC3 in the Dynhc interference+ rapamycin group was higher than that in the Dynhc interference group ( P<0.05). There were no statistically significant differences in the protein levels of Dynhc, α-synuclein, LAMP2, microtubule protein, p150 and KIF5B compared to the Dynhc interference group (all P>0.05). Compared with the control group, the cell apoptosis rate in PD group increased((12.77±1.66)%, (7.64±1.45)%), the microtubule morphology remained unchanged, and autophagosomes fused more with lysosomes. Compared with the PD group, the cell apoptosis rate of Dynhc overexpression group decreased, and there was no significant change in microtubule structure, and there was more fusion between autophagosomes and lysosomes.Compared with the PD group, the cell apoptosis rat of Dynhc interference group increased((18.45±1.91)%), and the microtubule morphology was sparse, and there was less fusion between autophagosomes and lysosomes. Compared with the PD group, the Dynhc overexpression group showed a decrease in cell apoptosis rate ((9.95±1.56)%), no significant changes in microtubule structure, and more fusion between autophagosomes and lysosomes.Compared with the Dynhc interference group, the Dynhc interference+ rapamycin group showed no significant changes in cell apoptosis rate ((19.05±2.46)%), microtubule morphology, and fusion of autophagosomes and lysosomes. Conclusion:Dynhc can reduce cell apoptosis by enhancing cell ALP function, increasing the degradation of α-synuclein and maintaining of microtubule structure integrity.

Correlation between plasma glial fibrillary acidic protein, α -synuclein and progression of Parkinson disease / 中华行为医学与脑科学杂志

Objective:To investigate the correlation between plasma glial fibrillary acidic protein (GFAP), total α-synuclein (α-syn), phosphorylated α-synuclein (p-α-syn) and the disease progression in patients with Parkinson disease(PD).Methods:Sixty-three patients with PD including the outpatients and inpatients from Department of Neurology of Huai'an First People's Hospital were continuously collected as a PD group, and 25 healthy people matched in age and sex were selected as a healthy control (HC) group at the same time. The plasma levels of GFAP, α-syn, and p-α-syn levels in the PD group and HC group were detected by ELISA. SPSS 25.0 software was used for statistical analysis. Mann-Whitney U test was performed to assess the differences of GFAP, α-syn and p-α-syn levels between the two groups, and the correlation between GFAP and α-syn and p-α-syn levels in PD group was examined by Spearman correlation analysis. The levels of GFAP, α-syn and p-α-syn in different Hoehn-Yahr(H-Y) stages of PD group were compared by Mann-Whitney U test and Spearman correlation analysis. Results:The levels of GFAP (0.80(0.62, 0.97)ng/mL, 0.54(0.27, 0.88)ng/mL, Z=-3.216, P=0.001), α-syn (3.93(3.16, 6.02)ng/mL, 2.67(1.74, 4.47)ng/mL, Z=-2.600, P=0.009), and p-α-syn (5.80(1.31, 15.62), 0.71(0.61, 0.83), Z=-6.607, P<0.001) in PD group were higher than those in HC group, and the difference was statistically significant. In PD group, there was a significant positive correlation between GFAP and α-syn ( r=0.442, P<0.001) and p-α-syn ( r=0.493, P<0.001). GFAP in the advanced PD group was higher than that in the early PD group, and the difference was statistically significant( P=0.039). There was no significant difference in α-syn and p-α-syn between different H-Y stages of PD patients( P>0.05). Plasma GFAP was positively correlated with H-Y stages ( r=0.277, P=0.018). Conclusion:The level of plasma GFAP in PD patients is positively correlated with disease progression, which can be used as a potential biomarker for PD disease assessment.

Phospholipid remodeling and Parkinson's disease / 药学学报

The remodeling of phospholipid includes two processes: deacylation and reacylation. It realizes the conversion of nascent phospholipids to mature phospholipids by changing the length and types of fatty acids at specific sites of phospholipids, which is a key step in phospholipid metabolism. Phospholipids are not only the basic components of biological membranes, but also participate in the transduction of many molecular signals in cells. Therefore, phospholipid remodeling disorders can affect the structure and function of cell membranes, as well as the activity of membrane proteins, causing a series of intricate signaling cascades, and finally lead to many pathological changes including neurodegeneration. This paper reviews the basic process of phospholipid remodeling and the involvement of its key enzymes, calcium independent group VIA phospholipase A2 (iPLA2β), peroxiredoxin 6 (PRDX6), calcium independent group VIB phospholipase A2 (iPLA2γ) as well as acyl-CoA lysocardiolipin acyltransferase 1 (ALCAT1) in the pathology of Parkinson's disease. The mutations in the gene encoding iPLA2β, PLA2G6, have been widely reported to be directly related to hereditary Parkinson disease-14 (PARK14). Here we focus on the molecular mechanism of iPLA2β in the development of Parkinson's disease, mainly involving phospholipid fatty acid metabolism disorders, mitochondrial physiology abnormalities and α-synuclein aggregate formation and other aspects, which will help to understand the role of phospholipid remodeling in Parkinson's disease, and provide new clues for the development of new Parkinson's disease diagnosis and treatment strategies.

Disease-modifying therapy for multiply system atrophy / 中华老年医学杂志

Multiple system atrophy(MSA)is a rare and fatal neurodegenerative disease occurring in middle-aged and older people, mainly characterized by autonomic nervous system and motor dysfunction.At present, there is no effective method to prevent or reverse its progression, and its treatment is mostly symptom-based, with limited success.A large number of interventional trials have been conducted to explore new treatments for MSA, but there is no clearly effective disease-modifying therapy, probably as a result of poor understanding of the pathophysiological and physiological mechanisms underlying MSA, which may be influenced by multiple factors.The purpose of this paper is to review the existing intervention trials for disease modification therapy of MSA and to discuss the outlook for new therapeutic targets.

Correlation between dementia with Lewy bodies and blood-brain barrier / 中华老年医学杂志

Dementia with Lewy bodies(DLB)is the second most common neurodegenerative dementia after Alzheimer's Disease(AD). This article will mainly elaborate the relationship between DLB and blood-brain barrier(BBB)from the following five aspects: (1)The structure and function of BBB; (2)In vivo assessment methods for the blood-brain barrier damage; (3)Evidence for the damage of blood-brain barrier in DLB; (4)The relationship between α-synuclein and the blood-brain barrier; (5)The relationship between APOE and the blood-brain barrier.Future research should focus on the pathogenesis of BBB damage in DLB patients, by which new drug targets for disease diagnosis and treatment may be found.

Clinical efficacy and mechanism of acupuncture for Parkinson's disease / 国际中医中药杂志

Acupuncture can improve the motor and non-motor symptoms of Parkinson's disease, and the effect of acupuncture combined with drug therapy is better than that of drug therapy alone. The possible mechanism includes inhibiting α-synuclein aggregation, oxidative stress, and neuroinflammation, inhibiting the apoptosis of dopaminergic neurons, and achieving a neuroprotective effect. The points mainly selected for Acupuncture treatment for this disease are Zusanli (ST 36), Yanglingquan (GB 34), Taichong (LR 3), Xuehai (SP 10), and other points. Early use of acupuncture and acupuncture combined with medical treatment strategy is worthy of clinical application.

The relationship between plasma phosphorylated α-synuclein and cognitive impairment in patients with Parkinson disease / 中华行为医学与脑科学杂志

Objective:To investigate the relationship between plasma phosphorylated α-synuclein (ps129-α-syn) and cognitive function in Parkinson disease (PD).Methods:This study recruited 90 PD patients who were hospitalized in the Department of Neurology, Henan province people's hospital from March 2019 to June 2020.Forty healthy middle-aged and elderly people with normal cognitive function who came to the hospital for physical examination were selected during the same period.Clinical characteristics and blood samples were collected.Patients with PD were classified into those with normally cognitive (PD-NC), mild cognitive impairment (PD-MCI), and dementia (PDD). The enzyme-linked immunosorbent assay was used to measure the plasma ps129-α-syn.Correlations between plasma ps129-α-syn and clinical characteristics such as disease duration, Hoehn-Yahr stage (H-Y), unified Parkinson's disease rating scale (UPDRS), Montreal cognitive assessment (MoCA), 14-item Hamilton anxiety rating scale (HAMA-14), the 24-item Hamilton depression rating scale (HAMD-24), levodopa equivalent daily dosage (LEDD), the scale of outcomes in Parkinson's disease for autonomic symptoms, SCOPA-AUT) were analyzed using Pearson or Spearman correlation analysis.Multiple linear regression analysis was used to evaluate the factors affecting the cognitive function of PD.Results:Plasma ps129-α-syn in PD patients was higher than that in healthy controls((19.44±8.93)μg/L, (10.78±5.87)μg/L, ( t=5.615, P<0.01). Plasma ps129-α-syn was higher in PD-MCI group((19.64±7.77)μg/L)and PDD group((23.79±9.47)μg/L) compared with that in PD-NC group((13.37±5.40)μg/L)( P<0.05). Plasma ps129-α-syn was positively correlated with H-Y ( r=0.404, P<0.01), UPDRS-Ⅲ( r=0.275, P=0.009), UPDRS-total ( r=0.211, P=0.046) and SCOPA-AUT( r=0.335, P=0.001). Plasma ps129-α-syn was negatively associated with MoCA ( r=-0.459, P<0.01). Multiple linear regression analysis suggested disease duration ( t=-4.618, P<0.01), ps129-α-syn( t=-3.792, P<0.01) and UPDRS-total ( t=-2.826, P=0.006) were independently associated with cognitive function.Plasma ps129-α-syn could discriminate between PD-NC and PD cognitive function impairment with an AUC of 0.7797 (95% CI: 0.686 3-0.873 2, P<0.01). Conclusions:Plasma ps129-α-syn is correlated with cognitive function and the severity of motor symptoms in PD patients, and have high sensitivity and specificity in diagnosing PD cognitive dysfunction.Therefore, plasma ps129-α-syn can serve as a biomarker to assess cognitive function in PD.