Speed of Pitch Change in People with Parkinson's Disease: A Pilot Study

Objective: To examine laryngeal maximum performance through a novel pitch diadochokinetic (DDK) task in people with Parkinson's disease (PD) and healthy controls. Methods: This exploratory pilot study included a total of eight people with PD (seven male and one female) and eight healthy controls. Participants were instructed to rapidly transition or alternate between a chosen comfortable low and high pitch and were instructed to complete the task as a pitch glide. An Auditory Sawtooth Waveform Inspired Pitch Estimator-Prime model was used to first extract the pitch contour and then a customized MATLAB algorithm was used to compute and derive measures of pitch range and pitch slope. Results: Pitch range and slope were reduced in some participants with PD. Effects of age and disease duration were observed in people with PD: reductions in both pitch measures with increase in age and disease duration. Conclusions: A novel pitch DDK task may supplement the conventional laryngeal DDK task in the evaluation and treatment of motor speech and voice disorders. Individual variability analysis may provide specific diagnostic and therapeutic insights for people with PD.

Objetivo: Examinar el máximo rendimiento laríngeo a través de una novedosa tarea diadococinética de tono (DDK, por sus siglas en inglés) en personas con enfermedad de Parkinson (EP) y controles sanos. Métodos: Este estudio piloto exploratorio incluyó un total de ocho personas con EP (siete hombres y una mujer) y ocho controles sanos. Se instruyó a los participantes para que hicieran una transición rápida o alternaran entre un tono bajo y uno alto que les resultara cómodo y se les indicó que completaran la tarea como un deslizamiento de tono. Se utilizó un modelo de Estimador de Tono Inspirado en la Forma de Onda de Diente de Sierra Auditiva-Prime para extraer primero el contorno del tono y luego se utilizó un algoritmo MATLAB personalizado para calcular y derivar medidas de rango de tono y pendiente de tono. Resultados: El rango y la pendiente de tono se redujeron en algunos participantes con EP. Se observaron efectos de la edad y la duración de la enfermedad en personas con EP: reducciones en ambas medidas de tono con el aumento de la edad y la duración de la enfermedad. Conclusiones: Una nueva tarea de DDK de tono podría complementar la tarea DDK laríngea convencional en la evaluación y el tratamiento de trastornos motores del habla y de la voz. El análisis de la variabilidad individual podría proporcionar información específica de diagnóstico y terapéutica para personas con EP.

Establishment and characterization of bone marrow mesenchymal stem cell lines stably synthesizing high-level dopamine / 生物工程学报

A triple-transgenic (tyrosine hydroxylase/dopamine decarboxylase/GTP cyclohydrolase 1, TH/DDC/GCH1) bone marrow mesenchymal stem cell line (BMSCs) capable of stably synthesizing dopamine (DA) transmitters were established to provide experimental evidence for the clinical treatment of Parkinson's disease (PD) by using this cell line. The DA-BMSCs cell line that could stably synthesize and secrete DA transmitters was established by using the triple transgenic recombinant lentivirus. The triple transgenes (TH/DDC/GCH1) expression in DA-BMSCs was detected using reverse transcription-polymerase chain reaction (RT-PCR), Western blotting, and immunofluorescence. Moreover, the secretion of DA was tested by enzyme-linked immunosorbent assay (ELISA) and high-performance liquid chromatography (HPLC). Chromosome G-banding analysis was used to detect the genetic stability of DA-BMSCs. Subsequently, the DA-BMSCs were stereotactically transplanted into the right medial forebrain bundle (MFB) of Parkinson's rat models to detect their survival and differentiation in the intracerebral microenvironment of PD rats. Apomorphine (APO)-induced rotation test was used to detect the improvement of motor dysfunction in PD rat models with cell transplantation. The TH, DDC and GCH1 were expressed stably and efficiently in the DA-BMSCs cell line, but not expressed in the normal rat BMSCs. The concentration of DA in the cell culture supernatant of the triple transgenic group (DA-BMSCs) and the LV-TH group was extremely significantly higher than that of the standard BMSCs control group (P < 0.000 1). After passage, DA-BMSCs stably produced DA. Karyotype G-banding analysis showed that the vast majority of DA-BMSCs maintained normal diploid karyotypes (94.5%). Moreover, after 4 weeks of transplantation into the brain of PD rats, DA-BMSCs significantly improved the movement disorder of PD rat models, survived in a large amount in the brain microenvironment, differentiated into TH-positive and GFAP-positive cells, and upregulated the DA level in the injured area of the brain. The triple-transgenic DA-BMSCs cell line that stably produced DA, survived in large numbers, and differentiated in the rat brain was successfully established, laying a foundation for the treatment of PD using engineered culture and transplantation of DA-BMSCs.

The Interaction Between CAL and mGluR1 Alleviates Cytotoxicity Induced by mGluR1 Overactivation / 中国生物化学与分子生物学报

Glutamate excitotoxicity mediated by metabotropic glutamate receptor 1 (mGluR1) overexpression or overactivation plays an important role in the development of Parkinson's disease (PD). Although clinical trials support the therapeutic potential of certain mGluR negative allosteric modulators (NAMs), there are still some limitations of precise modulation of mGluR using NAMs. Thus, the identification of small molecules or endogenous genes that facilitate mGluR1 modulation might be potentially beneficial for PD treatment. We determined the role of interacting partner cystic fibrosis transmembrane conductance regulator-associated ligand (CAL) in overactivated mGluR1-mediated cell apoptosis and signaling pathway in vitro and in vivo. HEK293 cells were used as an experimental tool to directly examine the interaction between CAL and mGluR1. We found that agonist of mGluR1 significantly enhanced the interaction between CAL and mGluR1 (P< 0. 05). Furthermore, CAL suppressed overactivated mGluR1-induced cell apoptosis and the activation of mGluR1 downstream signaling pathways. CAL overexpression relieved rotenone-induced neuron death (P< 0. 001) by inhibiting the activation of mGluR1-mediated signaling pathways in rotenone-induced rat model of PD. This study may reveal a new mechanism of mGluR1 activity regulation, and hopefully provide a novel molecular mechanism for the nervous system related diseases.

Lysosome TMEM175 Potassium Channel Protein and Parkinson’s Disease / 中国生物化学与分子生物学报

Parkinson’s disease (PD)is a complex neurodegenerative disorder by motor impairments and non-motor symptoms. While dopamine-based therapies are effective in fighting the symptoms in the early stages of the disease‚ a lack of neuroprotective drugs means that the disease continues to progress. New disease modifying therapies and novel therapeutic strategies are in high demand for PD patients. Genetic studies indicated that both rare and common genetic variants could induce the development PD. As a risk candidate gene for Parkinson’s disease‚ TMEM175 encodes a lysosomal potassium channel protein with new structures‚ and the protein plays an important role in maintaining lysosomal membrane potential and pH stability. With the in-depth understanding for its structure and function‚ TMEM175 deficiency results in decreased lysosomal catalytic activity and the pathological aggregation of α-synuclein. In view of the importance of lysosome potassium channel TMEM175‚ it could be an interesting target for the development of drugs to treat Parkinson’s disease and other neurodegenerative diseases. Herein we review the structure and function TMEM175‚ and focuses on its involvement in the occurrence and development of PD by affecting the function of lysosome as a homeostatic regulator. Future drug screenings based on lysosome TMEM175 may be carried out to maintain the active state or enhance the expression of TMEM175 to improve the condition of PD patients. Further investigations are needed to study how to maintain the balance between the open and closed state of TMEM175 channels to regulate the ion homeostasis of lysosomes. Studies of this ion channel protein will bring new strategies and ideas for the treatment of PD‚ and provide support for establishing the molecular status of TMEM175 in the diagnosis and treatment of PD.

Jiao's scalp acupuncture combined with virtual reality rehabilitation training for motor dysfunction in patients with Parkinson's disease: a randomized controlled trial / 中国针灸

OBJECTIVE@#To compare the clinical efficacy between Jiao's scalp acupuncture combined with virtual reality (VR) rehabilitation training and VR rehabilitation training alone for motor dysfunction in patients with Parkinson's disease (PD).@*METHODS@#A total of 52 patients with PD were randomly divided into an observation group and a control group, 26 cases in each group. The patients in both groups were treated with routine basic treatment, and the patients in the control group were treated with VR rehabilitation training. The patients in the observation group were treated with Jiao's scalp acupuncture on the basis of the control group. The scalp points included the movement area, balance area and dance tremor control area. Both groups were treated once a day, 5 times a week for a total of 8 weeks. Before treatment and 4 and 8 weeks into treatment, the gait parameters (step distance, step width, step speed and step frequency), timed "up and go" test (TUGT) time and unified Parkinson's disease rating scale part Ⅲ (UPDRS-Ⅲ) score were compared between the two groups, and the clinical efficacy was evaluated.@*RESULTS@#Four weeks into treatment, except for the step width in the control group, the gait parameters of the two groups were improved, the TUGT time was shortened, and the UPDRS-Ⅲ scores were reduced (P<0.01, P<0.05); the step distance in the observation group was better than that in the control group, and the UPDRS-Ⅲ score in the observation group was lower than that in the control group (P<0.05). Eight weeks into treatment, the gait parameters of the two groups were improved, the TUGT time was shortened, and the UPDRS-Ⅲ scores were reduced (P<0.01); the step distance and step speed in the observation group were better than those in the control group, the TUGT time in the observation group was shorter than that in the control group, and the UPDRS-Ⅲ score in the observation group was lower than that in the control group (P<0.05, P<0.01). The total effective rate was 92.3% (24/26) in the observation group, which was higher than 69.2% (18/26) in the control group (P<0.05).@*CONCLUSION@#Jiao's scalp acupuncture combined with VR rehabilitation training could improve the gait parameters, walking ability and motor function in patients with PD. The clinical effect is better than VR rehabilitation training alone.

Metabolic Disorder and Changes of Islet Morphology and Function in Thyl-aSYN Transgenic Mice / 中国生物化学与分子生物学报

Parkinson's disease (PD) is the second major neurodegenerative disease.The pathogenesis of PI) is still unclear.It is generally believed that neural damage, mitochondrial dysfunction, inflammation, oxidative stress and autophagy dysfunction caused by the transmission and aggregation of a- synuclein play an important role in the occurrence and development of PD.More and more research show- that metabolic disorder is one of the pathogenesis of PD.We examined whether overexpression of a- synuclein could induce metabolic disorder in mice and the possible mechanisms.Mice were divided into two groups: Thyl-aSYN transgenic mice (TG) and the control wild-type (WT) group.The rotarod test was used to analyze motor function in mice.We detected the body weight, plasma insulin content, glucose tolerance and insulin tolerance in the two group mice.The morphology of islets in the two groups were observed by hematoxylin eosin (HE) staining, and the islets were isolated to detect the glucose- stimulated insulin secretion (GSIS).The results showed that compared with the WT group, exercise tolerance of 12-month-old TG group decreased by 23.1% (P < 0.05) , body weight increased by 7% (P < 0.01), glucose tolerance decreased (P < 0.05), insulin tolerance decreased (P < 0.05), and insulin contents in the peripheral blood decreased by 20% (P < 0.05).Compared with the WT group, the levels of ce -syn proteins in the pancreas of the TG group increased by 1.32 times (P < 0.05) , the area of islets in the TG group decreased (P < 0.05 ) , the number of islets decreased (P < 0.01) , and the insulin secretion function decreased (P< 0.01).This study showed that the role of a-synuclein in PD is not limited to the damage of dopaminergic neurons, it also can affect metabolism and the morphology and function of peripheral organs, which provides a new theoretical basis for the pathogenesis of PD.

Parkin: an Extremely Versatile E3 Ubiquitin Ligase / 中国生物化学与分子生物学报

Parkin, also known as PARK2, has been closely related to Parkinson's disease (PD) since its discovery. It is considered to be a neuroprotective gene. With the in-depth understanding for its structure, Parkin has been unveiled as an E3 ubiquitin ligase. Parkin is involved in the regulation of cell cycle, mitochondrial homeostasis, energy metabolism and other cellular processes, and is closely related to many diseases. It even plays completely opposite roles in the same pathway, namely cell proliferation and apoptosis, indicating that this must be a gene with an extremely broad and important role. This article summarizes the discovery and structure of Parkin and its self-inhibiting characteristics, focusing on the ubiquitination process that it participates in as E3 ubiquitin ligase and the resulting autophagy, protein degradation, changes in protein subcellular localization and protein interaction. These may all serve as the basis for Parkin to prevent PD and suppress tumors. On this basis, two reasons for Parkin abnormalities leading to PD are summarized: abnormal protein quality control and mitochondrial dysfunction, and extended to cardiovascular and kidney diseases caused by the abnormality of Parkin due to mitochondrial dysfunction. The internal connection between Parkin and cancer is also introduced from the aspects of Parkin as a tumor suppressor, regulating cell cycle, apoptosis and metastasis, oxidative stress and energy metabolism. By maintaining the active state of Parkin or enhancing its expression, it may be possible to improve the condition of PD patients. But the mechanism of Parkin's inhibition of tumor growth remains to be deciphered, and the potential role of Parkin in mediating the relationship between PD and cancer risk should be strengthened. These follow-up in-depth studies and their role in the diagnosis and treatment of related diseases and application of target molecules laid the foundation.

Organic cation transporters in central nervous system diseases: research advances / 国际药学研究杂志

Organic cation transporters(OCT), one of the important members of membrane transporter family, can transport many kinds of positively charged substances and organic cation drugs used in physiological and pharmacological researches. A large number of studies have shown that the expression and function of OCT play an important role in the pathogenesis of some central nervous system(CNS)diseases, thus affecting the homeostasis of the internal environment. This article reviews the structure, substrate selectivity, tissue distribution and gene polymorphism of OCT in the CNS and provides a new possibility for the development of drugs targeting OCT and the clinical targeting of CNS diseases.

The therapeutic effect of quercetin on the transgenic PD drosophila model with LRRK2 mutation / 西安交通大学学报(医学版)

Objective: To study the therapeutic effect and mechanism of quercetin on Parkinson's disease (PD) model induced by a leucine-rich repeat kinase 2 (LRRK2) gene mutation. Methods: PD transgenic drosophila model Ddc-Gal4; UAS-LRRK2/G2019S was generated by Gal4/UAS hybridization and selectively expressed G2019S mutant LRRK2 in dopaminergic neurons. PD transgenic drosophila and control were fed with corn medium supplemented with quercetin in 1, 10 and 100 μmol/L for the treatment group, or with standard corn medium in PD model group and blank control group. The life span and locomotor ability were observed and compared between the quercetin treatment group and the PD drosophila model group. The brains of the drosophila were dissected and stained with TH immunofluorescence antibody to observe the survival rate of dopaminergic neurons. The brain tissues were also measured with Western blot to detect the protein expression levels of TH, GCLC, p-LRRK2, and p-p38MAPK. Results: The group treated with 10 μmol/L quercetin showed the best therapeutic effect on the prolongation of life span and improvement of locomotor ability compared with PD transgenic drosophila model without any treatment. The locomotor activity of drosophila was significantly improved at week 6 and the loss of dopaminergic neurons in the brain of the PD model drosophila was effectively diminished by quercetin. Quercetin also significantly lowered the level of phosphorylated LRRK2 in the PD transgenic drosophila compared with the PD model group (P<0.05), indicating the inhibiting effect of quercetin on the activity of LRRK2 kinase of the PD model. In addition, quercetin could activate the antioxidant-signaling pathway and inhibit the p38MAPK signaling pathway. Results: Quercetin can activate the antioxidant-signaling pathway and inhibit the LRRK2 kinase activity, which can further regulate MAPK signaling pathway and reduce the neurotoxicity of LRRK2 mutation and protect dopaminergic neurons in PD transgenic drosophila model.

Imaging law of postoperative electrode locations in deep brain stimulation for Parkinson's disease / 上海交通大学学报（医学版）

Objective:To explore the potential regularity and cause of the differences between magnetic resonance imaging (MRI) and computed tomography (CT) presenting electrodes after deep brain stimulation (DBS) for Parkinson's disease (PD), in order to provide reference for optimizing clinical decision. Methods:Forty-nine PD patients who underwent DBS treatment in Department of Functional Neurosurgery of Ruijin Hospital, Shanghai Jiao Tong University School of Medicine from Jan. 2016 to Dec. 2017 were selected. CT images were acquired 3-5 days after surgery and MRI images were acquired during 3-6 months by the follow-up of regular programming. The fused images of short-term CT combined with preoperative MRI and long-term MRI respectively were compared to show the difference by the tip contact positions of electrodes. Results:A total of 50 groups of postoperative CT fused images and MRI images were obtained. The space differences of the two types of images were 1.36 (0.98, 1.70) mm (P=0.021) and 1.28 (0.99, 1.88) mm (P=0.006), on the right and left electrodes, respectively. Bilateral electrodes in both short-term and long-term images had a tendency to move to the medial, rear, and bottom part of the brain. Conclusion:The potential tendency in shifts of DBS electrodes can provide reference for establishing the brain drift model and optimizing the position of the implanted electrode.

Cut-off points of the Portuguese version of the Montreal Cognitive Assessment for cognitive evaluation in Parkinson's disease / Valores de corte da versão em português do "montreal cognitive assessment" para avaliação cognitiva na doença de parkinson

ABSTRACT. The Movement Disorder Society has published some recommendations for dementia diagnosis in Parkinson disease (PD), proposing the Montreal Cognitive Assessment (MOCA) as a cognitive screening tool in these patients. However, few studies have been conducted assessing the Portuguese version of this test in Brazil (MOCA-BR). Objective: the aim of the present study was to define the cut-off points of the MOCA-BR scale for diagnosing Mild Cognitive Impairment (PD-MCI) and Dementia (PD-D) in patients with PD. Methods: this was a cross-sectional, analytic field study based on a quantitative approach. Patients were selected after a consecutive assessment by a neurologist, after an extensive cognitive evaluation, and were classified as having normal cognition (PD-N), PD-MCI or PD-D. The MOCA-BR was then applied and 89 patients selected. Results: on the cognitive assessment, 30.3% were PD-N, 41.6% PD-MCI and 28.1% PD-D. The cut-off score on the MOCA-Br to distinguish PD-N from PD-D was 22.50 (95% CI 0.748-0.943) for sensitivity of 85.5% and specificity of 71.1%. The cut-off for distinguishing PD-D from MCI was 17.50 (95% CI 0.758-0.951) for sensitivity of 81.6% and specificity of 76%.

RESUMO. A Movement Disorder Society publicou algumas recomendações para o diagnóstico de demência na doença de Parkinson (DP), propondo o Montreal Cognitive Assessment (MOCA) como ferramenta de triagem cognitiva nesses pacientes. Entretanto, poucos estudos foram aplicados à versão em português (MOCA-BR). Objetivo: o presente estudo tem o objetivo de definir os valores de corte na escala de MOCA-BR para diagnosticar o Comprometimento Cognitivo Leve (DP-CCL) e Demência (DP-D) em pacientes com DP. Métodos: trata-se de um estudo transversal, analítico, com uma abordagem quantitativa. Os pacientes foram selecionados depois de avaliações consecutivas por um neurologista, após avaliação cognitiva extensa, e foram classificados como cognição normal (DP-N), DP-CCL e DP-D e então o MOCA-BR foi aplicado, sendo selecionados 89 pacientes. Resultados: na avaliação cognitiva, foram encontrados 30.3% de DP-N, 41.6% de DP-CCL e 28.1% DP-D. O valor de corte no MOCA-BR para distinguir entre DP-N de DP-D foi 22.5 (IC 95%; 0.748-0.943), sensibilidade de 85.5% e especificidade de 71.1%. Para distinguir DP-P de CCL, o ponto de corte foi de 17.5 (IC 95%; 0.758-0.951), sensibilidade de 81.6% e especificidade de 76%.

HDAC Inhibition by Valproic Acid Induces Neuroprotection and Improvement of PD-like Behaviors in LRRK2 R1441G Transgenic Mice

Parkinson’s disease (PD) is one of the late-onset neurodegenerative movement disorder. Major pathological markers of PD include progressive loss of dopaminergic neurons, Lewy body formation, genetic mutations, and environmental factors. Epigenetic regulation of specific gene expression via impaired histone acetylation is associated with neuronal dysfunction in various neurodegenerative diseases. In this study, we hypothesized that histone deacetylase (HDAC) inhibitor, valproic acid (VPA), can improve motor function by enhancing cell survival in PD genetic model mice with LRRK2 R1441G mutation. To address this question, we administered VPA in LRRK2 R1441G transgenic mice to determine whether VPA affects 1) histone acetylation and HDAC expression, 2) dopaminergic neuron survival, 3) inflammatory responses, 4) motor or non-motor symptoms. As results, VPA administration increased histone acetylation level and the number of tyrosine hydroxylase (TH) positive neurons in substantia nigra of LRRK2 R1441G mice. VPA reduced iba-1 positive activated microglia and the mRNA levels of pro-inflammatory marker genes in LRRK2 R1441G mice. In addition, VPA induced the improvement of PD-like motor and non-motor behavior in LRRK2 R1441G mice. These data suggest that the inhibition of HDAC can be further studied as potential future therapeutics for PD.

PARKINSON’S DISEASE IN THE ELDERLY

@#Parkinson’s disease (PD) is the second most common neurodegenerative disorder globally and its prevalence in Singapore is expected to increase exponentially with our ageing population. Diagnostic and management issues unique to the elderly population will be discussed broadly in this topic review.

Effects of chaperone-mediated autophagy on the level of α-synuclein oligomers in Parkinson's disease cell model / 上海交通大学学报（医学版）

Objective • To investigate the effects of chaperone-mediated autophagy (CMA) on α-synuclein oligomers level in the Parkinson's disease (PD) cell model with impaired ubiquitin proteasome system (UPS). Methods • The PD cell model was established by adding the proteasome inhibitor lactacystin in the SK-N-SH cell line stably transfected with wild type α-synuclein. The levels of α-synuclein oligomers, lysosome-associated membrane protein type 2A (LAMP2A) and 70 kDa heat shock homologous protein (HSC70) were detected using Western blotting. CMA function was inhibited with LAMP2A siRNA, and its effects on α-synuclein oligomers and cell viability were detected. Furthermore, the interaction of LAMP2A with α-synuclein oligomers was detected by immunoprecipitation. Results • In the PD cell model, the levels of α-synuclein oligomers, and CMA related proteins, i.e. LAMP2A and HSC70, were increased. Inhibiting the expression of LAMP2A further increased α-synuclein oligomers level, while it decreased cell viability. Furthermore, LAMP2A could interact with α-synuclein oligomers. Conclusion • In the PD cell model, CMA is one of the pathways regulating α-synuclein oligomers level. Inhibiting CMA function can further increase the α-synuclein oligomers level and deteriorate cell survival.

Effects of treatment on ultrastructure of olfactory bulb and GFAP expression in mice with Parkinson's disease / 中国针灸

OBJECTIVE@#To observe the effects of treatment on the ultrastructure of olfactory bulb and the expression of substantia nigra glial fibrillary acidic protein (GFAP) in mice with Parkinson's disease (PD) induced by lipopolysaccharide (LPS), and to provide methods and evidence for early prevention and treatment of PD.@*METHODS@#Forty C57BL/6 male mice were randomly divided into a blank group, a model group, an electroacupuncture (EA) group and a medication group, 10 mice in each one. The mice in the model group, EA group and medication group were treated with 30-day nasal perfusion of LPS to establish PD model. From the first day of model establishment, the mice in the EA group were treated with electroacupuncture at bilateral "Yingxiang" (LI 20) and "Yintang" (GV 29) for 20 min, once a day; 5-day treatment was taken as one session, and 4 sessions were given with an interval of 2 days between sessions. The mice in the medication group were treated with intraperitoneal injection of L-DOPA, 10 mg/mL, once a day; 5-day treatment was taken as one session, and 4 sessions were given with an interval of 2 days between sessions. After treatment, the behavioristics changes were observed by using footprint analysis and swimming test score; the ultrastructure of olfactory bulb was observed by using transmission electron microscopy; the expression of GFAP in substantia nigra was measured by using western blot method.@*RESULTS@#① After model establishment, the mice in the model group, the EA group and medication group showed significant symptoms of quiver and fear of chill, and the BMI was significantly lower than that in the blank group (all 0.05). ③ After treatment, the footprint and swimming time in the model group were significantly lower than that in the blank group (both <0.01); the footprint and swimming time in the EA group and medication group were significantly higher than those in the model group (all <0.01).④ After treatment, compared with the blank group, the organelles and ultrastructure of olfactory bulb in the model group were significantly improved; the ultrastructure of olfactory bulb in the EA group was improved compared with that in the model group. ⑤ After treatment, the expression of substantia nigra GFAP in the model group was significantly higher than that in the blank group (<0.01); the expression of substantia nigra GFAP in the EA group and medication group was significantly lower than that in the model group (both <0.05).@*CONCLUSION@#The early treatment of can improve behavioral disorders in LPS-induced early PD mice, and the mechanism may be related to the regulation of olfactory disorders and the expression of GFAP in substantia nigra.

Research advances in acetylation modification of α-synuclein in Parkinson's disease / 上海交通大学学报（医学版）

Parkinson's disease (PD) is an incurable neurodegenerative disease, which seriously affects the life quality of patients. Researches in recent years found that excessive production or abnormal structure of α-synuclein and forming toxic aggregates are the key factors in the pathogenesis of PD. In a variety of mechanisms, abnormal modification of α-synuclein is closely related to its aggregation state, such as phosphorylation, ubiquitination and nitration modification, but the exact effects are still uncertain. Recent studies have shown that acetylation modification of α-synuclein plays an important role in the abnormal aggregation of α-synuclein. This article reviewed the progress of acetylation modification of α-synuclein.

Parkinson's Disease Impulsive-Compulsive Disorders Questionnaire - Current Short (QUIP-CS) - Translation and validation of content of Portuguese Version / Parkinson's Disease Impulsive-Compulsive Disorders Questionnaire - Current Short (QUIP-CS) - Tradução e validação de conteúdo em português do Questionário para Avaliação de Distúrbios Impulsivo-Compulsivos na Doença de Parkinson

ABSTRACT Objective Parkinson's disease (PD) management is usually successfully reached with proper pharmacological treatment. However, PD patients can manifest neuropsychiatric symptoms secondary to medical therapy, including impulse control disorders (ICD), presenting as pathological gambling, hypersexuality, compulsive buying, drinking or eating disorders. We translated and validated the Portuguese version of the gold-standard questionnaire Parkinson's Disease Impulsive-Compulsive Disorders Questionnaire, or (QUIP) for identifying ICDs in PD patients. Methods Translation, back translation and submission to instrument developer was performed, that approved its new version comparing it to his original, validated version, with no loss of it's original properties. Then, the Portuguese version was administered to 30 PD patients. They also were asked to rate from 1 to 5 the level of comprehensibility of the questions. Results The average level of comprehension was 4.06 ± 0.69 DP, considering 3 or more as acceptable. No patient has answered 1 or 2. Conclusion Our results on Portuguese version of QUIP-CS show that QUIP-CS translated and corrected version was easily understood and easily self-applied.

RESUMO Objetivo O manejo da doença de Parkinson (DP) é usualmente alcançado com sucesso com o tratamento farmacológico apropriado. Entretanto, os pacientes com DP podem manifestar sintomas neuropsiquiátricos secundários à terapêutica, como a síndrome de descontrole dos impulsos (SDI), que se apresenta como o jogar patológico, a hipersexualidade, o comprar, beber ou comer compulsivos. Traduzimos e validamos a versão em português do questionário padrão-ouro para identificação de transtornos impulsivo-compulsivos na DP (QUIP-CS) para identificar nesses pacientes a presença de SDI. Métodos Foram realizadas a tradução, a retrotradução e a submissão do instrumento ao desenvolvedor deste, que aprovou a nova versão comparando esta à sua, que já está validada, sem a perda das suas propriedades originais. Após, a versão em português foi administrada a 30 pacientes com o diagnóstico de DP. Eles também foram solicitados a classificar o nível de compreensibilidade das questões, graduando-as de 1 a 5. Resultados O nível médio de compreensão foi 4,06 ± 0,69 DP, considerando-se 3 ou mais como aceitável. Nenhum paciente respondeu 1 ou 2. Conclusão Os nossos resultados para a versão em português da QUIP-CS mostraram que essa versão, traduzida e corrigida, foi facilmente compreendida e aplicada pelos próprios pacientes.

La Enfermedad de Parkinson: Etiología, Tratamientos y Factores Preventivos / Parkinson Disease: Etiology, Treatments and Preventive Factors

La enfermedad de Parkinson (EP) es la patología neurodegenerativa motora con mayor incidencia a nivel mundial, cuyas causas aún no son claras. Actualmente no existe cura, pero es posible contar con diferentes tratamientos que permiten aliviar algunos de sus síntomas y enlentecer su curso. Debido a la gran cantidad de informaciones, en ocasiones contradictorias sobre los llamados "factores de riesgo" (entendidos éstos como situaciones que pueden exacerbar la posibilidad de aparición de la enfermedad, incluyendo desde la predisposición familiar hasta la exposición prolongada a substancias exógenas), en esta revisión se pretende ofrecer una panorámica actual sobre factores asociados a la aparición de EP Se revisan también algunos tratamientos que buscan contrarrestar la pérdida de la función dopaminérgica de la substancia nigra (SN) y algunas de las aproximaciones terapéuticas tanto farmacológicas, como por estimulación cerebral profunda (ECP) o por implante celular. Se revisan también investigaciones sobre el potencial terapéutico de compuestos con alta especificidad a receptores colinérgicos (nAChRs) y antagonistas de receptores de adenosina, específicamente del subtipo A2A. Posiblemente durante las próximas décadas, nuestro conocimiento en epigenética pueda arrojar nuevas luces sobre esta interacción, así como sobre las relaciones entre ciertas líneas de microbios intestinales y aparición de EP. En este momento, la alternativa terapéutica que ofrece mayor eficacia es la ECP, sin embargo, a futuro se espera que el desarrollo de nuevas estrategias de implante cerebral pueda ofrecer una cura real de la EP.

Parkinson's disease (PD) is the most prevalent neurodegenerative motor pathology worldwide, the causes of which are still unclear. Currently there is no cure, but it is possible to have different treatments that allow to alleviate some of its symptoms and slow its course. Due to the large amount of information, sometimes contradictory, about the so-called "risk factors" (understood as situations that may exacerbate the possibility of the onset of the disease, from family predisposition to prolonged exposure to exogenous substances), in this review aims to provide a current overview of factors associated with the occurrence of PD. We also review some treatments that seek to counteract the loss of the dopaminergic function of the substance nigra (SN) and some of the therapeutic approaches both pharmacologically, by deep brain stimulation (DBS) or by cellular implantation. Also reviewed investigations on the therapeutic potential of compounds with high specificity to cholinergic receptors (nAChRs) and adenosine receptor antagonists, specifically the A2A subtype. Possibly, during the next decades, our knowledge in epigenetics may shed new light on this interaction, as well as on the relationships between certain lines of intestinal microbes and onset of PD. At this time, the most effective therapeutic alternative is DBS; however, in the future it is expected that the development of new brain implant strategies may offer a real cure for PD.

Clock drawing test to screen for dementia in parkinsonian patients with low educational backgrounds

Objectives: This study was aimed to assess the usefulness of the quantitative assessment of clock drawing test (CDT) combined with the Mini-Mental State Examination (MMSE) compared to that of the Montreal Cognitive Assessment (MoCA) or the MMSE alone for screening of dementia in Parkinson disease (PD) in patients with a low educational level. Methods: A representative sample of 91 PD patients was administered MMSE, MoCA and CDT. The discriminative validity of the MMSE, MoCA, and a MMSE+CDT combination for dementia screening was determined by estimating the sensitivity and specificity of each test and by testing integrated discrimination improvement (IDI). Results: The mean age and educational years were 69.0 (years) and 7.3 in the study population. The best screening cut-off points for the MMSE, MoCA, and MMSE+CDT were 25/26, 21/22 and 41/42. In a group of patients with educational years ≤6,

Relationship between serum high-sensitivity C-reactive protein levels and cognitive function in patients with Parkinson’s disease

Inflammation might be associated with cognitive impairment and be involved in the pathogenesis of Parkinson’s disease (PD). High-sensitivity C-reactive protein (hs-CRP) is a sensitive biomarker of systemic inflammation. This study aimed to investigate whether serum concentrations of hs-CRP are related to cognitive function in patients with PD. Patients with PD (n = 113, Hoehn and Yahr [H-Y] stage 1-4) underwent evaluation of serum hs-CRP and comprehensive neuropsychological tests that covered the cognitive domains of attention, language, visuospatial function, memory, and executive functions. We categorized subjects with PD as having normal cognition (n=48), mild cognitive impairment (MCI) (n=41), or dementia (n=24). Patients with dementia had a higher hs-CRP level than patients with MCI or normal cognition (2.76 ± 2.53 vs. 1.27 ± 1.99 vs. 0.73 ± 0.88 mg/L, P=0.001). Serum hs-CRP levels were inversely associated with the Mini-Mental State Examination scores and performance on neuropsychological tests of language, visuospatial function, visual memory, and executive function. After controlling for age, sex, symptom duration, education, H-Y stage, and Unified Parkinson’s Disease Rating Scale motor score, multiple regression analyses indicated statistically significant associations between hs-CRP levels and performance on neuropsychological tests of visuospatial function, visual memory, and executive function. This study suggests a possible relationship between serum hs-CRP levels and cognitive function in patients with PD, with higher levels of hs-CRP being associated with poor performance on tests of visuospatial function, visual memory, and executive function.