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Parkinson's Disease Multimodal Complex Treatment improves motor symptoms, depression and quality of life.


  • 影响因子:3.21
  • DOI:10.1007/s00415-019-09657-7
  • 作者列表:"Scherbaum R","Hartelt E","Kinkel M","Gold R","Muhlack S","Tönges L
  • 发表时间:2020-04-01

:Parkinson's disease (PD) is the world's fastest growing neurological disorder disabling patients through a broad range of motor and non-motor symptoms. For the clinical management, a multidisciplinary approach has increasingly been shown to be beneficial. In Germany, inpatient Parkinson's Disease Multimodal Complex Treatment (PD-MCT) is a well-established and frequent approach, although data on its effectiveness are rare. We conducted a prospective real-world observational study in 47 subjects [age (M ± SD): 68.5 ± 9.0 years, disease duration: 8.5 ± 5.3 years, modified Hoehn and Yahr stage (median, IQR): 3, 2.5-3] aiming at evaluating the effectiveness of 14-day PD-MCT in terms of quality of life (Parkinson's Disease Questionnaire, EuroQol), motor [Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS III], Timed Up and Go Test, Purdue Pegboard Test) and non-motor symptoms (revised Beck Depression Inventory). Six weeks after hospital discharge, a follow-up examination was performed. PD patients with a predominantly moderate disability level benefited from PD-MCT in terms of health-related quality of life, motor symptoms and non-motor symptoms (depression). Significant improvements were found for social support, emotional well-being and bodily discomfort domains of health-related quality of life. Sustainable improvement occurred for motor symptoms and the subjective evaluation of health state. We found a higher probability of motor response especially for patients with moderate motor impairment (MDS-UPDRS III ≥ 33). In conclusion, Parkinson's Disease Multimodal Complex Treatment improves motor symptoms, depression and quality of life. A more detailed selection of patients who will benefit best from this intervention should be examined in future studies.


: 帕金森病 (Parkinson's disease,PD) 是世界上发展最快的神经系统疾病,通过广泛的运动和非运动症状致残患者。对于临床管理,多学科方法越来越被证明是有益的。在德国,住院帕金森病多模式综合治疗 (PD-MCT) 是一种成熟和频繁的方法,尽管关于其有效性的数据很少。我们在 47 名受试者中进行了一项前瞻性真实世界观察性研究 [年龄 (m ± sd): 68.5 ± 9.0 年,病程: 8.5 ± 5.3 年,改良 Hoehn 和 Yahr 分期 (中位数,IQR): 3, 2.5-3] 旨在评估 14 天 PD-MCT 在生活质量方面的有效性 (帕金森病问卷,EuroQol),运动障碍 [运动障碍学会统一帕金森氏病评定量表第三部分 (MDS-UPDRS III],计时加和去测试,Purdue Pegboard 测试) 和非运动症状 (修订的贝克抑郁量表)。出院 6 周后进行随访检查。以中度残疾水平为主的 PD 患者在健康相关生活质量、运动症状和非运动症状 (抑郁) 方面受益于 PD-MCT。发现健康相关生活质量的社会支持、情绪幸福感和身体不适领域有显著改善。运动症状和健康状态的主观评价出现可持续改善。我们发现运动反应的概率更高,特别是对于中度运动损伤患者 (MDS-UPDRS ⅲ i ≥ 33)。总之,帕金森病多模式综合治疗可改善运动症状、抑郁和生活质量。在未来的研究中应检查更详细的选择将从这种干预中获益最好的患者。



作者列表:["Aimé P","Karuppagounder SS","Rao A","Chen Y","Burke RE","Ratan RR","Greene LA"]

METHODS::Identifying disease-causing pathways and drugs that target them in Parkinson's disease (PD) has remained challenging. We uncovered a PD-relevant pathway in which the stress-regulated heterodimeric transcription complex CHOP/ATF4 induces the neuron prodeath protein Trib3 that in turn depletes the neuronal survival protein Parkin. Here we sought to determine whether the drug adaptaquin, which inhibits ATF4-dependent transcription, could suppress Trib3 induction and neuronal death in cellular and animal models of PD. Neuronal PC12 cells and ventral midbrain dopaminergic neurons were assessed in vitro for survival, transcription factor levels and Trib3 or Parkin expression after exposure to 6-hydroxydopamine or 1-methyl-4-phenylpyridinium with or without adaptaquin co-treatment. 6-hydroxydopamine injection into the medial forebrain bundle was used to examine the effects of systemic adaptaquin on signaling, substantia nigra dopaminergic neuron survival and striatal projections as well as motor behavior. In both culture and animal models, adaptaquin suppressed elevation of ATF4 and/or CHOP and induction of Trib3 in response to 1-methyl-4-phenylpyridinium and/or 6-hydroxydopamine. In culture, adaptaquin preserved Parkin levels, provided neuroprotection and preserved morphology. In the mouse model, adaptaquin treatment enhanced survival of dopaminergic neurons and substantially protected their striatal projections. It also significantly enhanced retention of nigrostriatal function. These findings define a novel pharmacological approach involving the drug adaptaquin, a selective modulator of hypoxic adaptation, for suppressing Parkin loss and neurodegeneration in toxin models of PD. As adaptaquin possesses an oxyquinoline backbone with known safety in humans, these findings provide a firm rationale for advancing it towards clinical evaluation in PD.

翻译标题与摘要 下载文献
作者列表:["Sebastián-Serrano Á","Simón-García A","Belmonte-Alfaro A","Pose-Utrilla J","Santos-Galindo M","Del Puerto A","García-Guerra L","Hernández IH","Schiavo G","Campanero MR","Lucas JJ","Iglesias T"]

METHODS::Huntington's disease (HD) is an inherited progressive neurodegenerative disease characterized by brain atrophy particularly in the striatum that produces motor impairment, and cognitive and psychiatric disturbances. Multiple pathogenic mechanisms have been proposed including dysfunctions in neurotrophic support and calpain-overactivation, among others. Kinase D-interacting substrate of 220 kDa (Kidins220), also known as ankyrin repeat-rich membrane spanning (ARMS), is an essential mediator of neurotrophin signaling. In adult brain, Kidins220 presents two main isoforms that differ in their carboxy-terminal length and critical protein-protein interaction domains. These variants are generated through alternative terminal exon splicing of the conventional exon 32 (Kidins220-C32) and the recently identified exon 33 (Kidins220-C33). The lack of domains encoded by exon 32 involved in key neuronal functions, including those controlling neurotrophin pathways, pointed to Kidins220-C33 as a form detrimental for neurons. However, the functional role of Kidins220-C33 in neurodegeneration or other pathologies, including HD, has not been explored. In the present work, we discover an unexpected selective downregulation of Kidins220-C33, in the striatum of HD patients, as well as in the R6/1 HD mouse model starting at early symptomatic stages. These changes are C33-specific as Kidins220-C32 variant remains unchanged. We also find the early decrease in Kidins220-C33 levels takes place in neurons, suggesting an unanticipated neuroprotective role for this isoform. Finally, using ex vivo assays and primary neurons, we demonstrate that Kidins220-C33 is downregulated by mechanisms that depend on the activation of the protease calpain. Altogether, these results strongly suggest that calpain-mediated Kidins220-C33 proteolysis modulates onset and/or progression of HD.

翻译标题与摘要 下载文献
作者列表:["Mendes FR","Leclerc JL","Liu L","Kamat PK","Naziripour A","Hernandez D","Li C","Ahmad AS","Doré S"]

METHODS:BACKGROUND:Neuroinflammation has been recognized as an important factor in the pathogenesis of Alzheimer's disease (AD). One of the most recognized pathways in mediating neuroinflammation is the prostaglandin E2-EP1 receptor pathway. OBJECTIVE:Here, we examined the efficacy of the selective EP1 antagonist ONO-8713 in limiting amyloid-β (Aβ), lesion volumes, and behavioral indexes in AD mouse models after ischemic stroke. METHODS:Transgenic APP/PS1, 3xTgAD, and wildtype (WT) mice were subjected to permanent distal middle cerebral artery occlusion (pdMCAO) and sham surgeries. Functional outcomes, memory, anatomical outcomes, and Aβ concentrations were assessed 14 days after surgery. RESULTS:pdMCAO resulted in significant deterioration in functional and anatomical outcomes in the transgenic mice compared with the WT mice. No relevant differences were observed in the behavioral tests when comparing the ONO-8713 and vehicle-treated groups. Significantly lower cavitation (p = 0.0373) and percent tissue loss (p = 0.0247) were observed in APP/PS1 + ONO-8713 mice compared with the WT + ONO-8713 mice. However, the percent tissue injury was significantly higher in APP/PS1 + ONO-8713 mice compared with WT + ONO-8713 group (p = 0.0373). Percent tissue loss was also significantly lower in the 3xTgAD + ONO-8713 mice than in the WT + ONO-8713 mice (p = 0.0185). ONO-8713 treatment also attenuated cortical microgliosis in APP/PS1 mice as compared with the vehicle (p = 0.0079); however, no differences were observed in astrogliosis across the groups. Finally, APP/PS1 mice presented characteristic Aβ load in the cortex while 3xTgAD mice exhibited very low Aβ levels. CONCLUSION:In conclusion, under the experimental conditions, EP1 receptor antagonist ONO-8713 showed modest benefits on anatomical outcomes after stroke, mainly in APP/PS1 mice.