Parkinson's Disease最新文献

Objectives: The aim of this study was to investigate the impact of nonmotor symptoms (NMS) on the quality of life (QoL) outcome after subthalamic nucleus deep brain stimulation (STN-DBS) at the 1-year follow-up.

Methods: Ninety-three patients diagnosed with Parkinson's disease (PD), who underwent subthalamic nucleus deep brain stimulation (STN-DBS) between April 2020 and August 2021, were included in this study. Demographic information was gathered through a self-designed questionnaire. The severity of both motor and non-motor symptoms, along with the quality of life (QoL), was assessed using the Unified Parkinson's Disease Rating Scale-III (UPDRS-III), Nonmotor Symptoms Scale (NMSS), and 8-item Parkinson's Disease Questionnaire (PDQ-8), respectively.

Results: Significant differences were observed in the UPDRS-III score, NMSS summary index (SI), and subscores of six domains (sleep/fatigue, mood/cognition, perceptual problems/hallucinations, attention/memory, urinary, and sexual function) between the baseline and the 6- and 12-month follow-ups. The correlation analysis revealed positive correlations between the preoperative NMSS SI and subscores of seven domains (cardiovascular, sleep/fatigue, mood/cognition, perceptual problems/hallucinations, attention/memory, gastrointestinal, and urinary) and ΔPDQ-8. Moreover, the preoperative PDQ-8 SI (β = 0.869, P < 0.001) and the preoperative attention/memory subscore (β = -0.154, P = 0.026) were predictive of the postsurgery improvement in quality of life (QoL).

Conclusion: Deep brain stimulation (DBS) led to an improvement in the patients' nonmotor symptoms (NMS) at the 1-year follow-up, along with a correlation observed between NMS and the patients' quality of life (QoL). Notably, the severity of preoperative attention/memory problems emerged as the most significant predictor of NMS influencing the QoL outcome after STN-DBS at the 1-year follow-up.

Background: Rising from a chair or the sit-to-stand (STS) task is frequently impaired in individuals with Parkinson's disease (PD). These patients commonly attribute such difficulties to weakness in the lower extremities. However, the role of muscle strength in the STS transfer task has not been fully elucidated.

Objective: We aim at determining the role of muscle strength in the STS task.

Methods: We studied 90 consecutive patients with PD and 52 sex- and age-matched controls. Lower limb strength was determined in both legs by clinical examination using the Medical Research Council Scale, dynamometric (leg flexion) and weighting machine (leg pressure) measures. Patients were interrogated regarding the presence of subjective lower limb weakness or allied sensations.

Results: There were 20 patients (22.2%) with abnormal STS task (item 3.9 of the MDS-UPDRS-III ≥2 points). These patients had higher modified Hoehn and Yahr stage (P  <  0.001) and higher total motor scores of the MDS-UPDRS(P  <  0.001), compared with 70 PD patients with normal STS task. Patients with abnormal STS task endorsed lower limb weakness more frequently and had lower muscle strength in the proximal lower extremities, compared to PD patients with normal STS task and normal controls. The presence of perceived lower limb weakness increased the risk of an abnormal STS task, OR: 11.93 (95% C.I. 1.51-94.32), whereas a hip extension strength ≤9 kg/pressure also increased the risk of abnormal STS task, OR: 4.45 (95% C.I. 1.49-13.23). In the multivariate regression analysis, bradykinesia and decreased hip strength were related to abnormal STS task.

Conclusions: Patients with PD and abnormal STS task complain more commonly of lower limb weakness and have decreased proximal lower limb strength compared to patients with PD and normal STS task, likely contributing to abnormalities in performing the STS task.

Adenosine 5'-monophosphate-activated protein kinase (AMPK)'s effect in PTEN-induced kinase 1 (PINK1) mutant Parkinson's disease (PD) transgenic flies and the related mechanism is seldom studied. The classic MHC-Gal4/UAS PD transgenic flies was utilized to generate the disease characteristics specifically expressed in flies' muscles, and Western blot (WB) was used to measure the expression of the activated form of AMPK to investigate whether activated AMPK alters in PINK1^B9 PD flies. MHC-Gal4 was used to drive AMPK overexpression in PINK1^B9 flies to demonstrate the crucial role of AMPK in PD pathogenesis. The abnormal wing posture and climbing ability of PINK1^B9 PD transgenic flies were recorded. Mitochondrial morphology via transmission electron microscopy (TEM) and ATP and NADH: ubiquinone oxidoreductase core subunit S3 (NDUFS3) protein levels were tested to evaluate the alteration of the mitochondrial function in PINK1^B9 PD flies. Phosphorylated AMPKα dropped significantly in PINK1^B9 flies compared to controls, and AMPK overexpression rescued PINK^B9 flies' abnormal wing posture rate. The elevated dopaminergic neuron number in PPL1 via immunofluorescent staining was observed. Mitochondrial dysfunction in PINK1^B9 flies has been ameliorated with increased ATP level, restored mitochondrial morphology in muscle, and increased NDUFS3 protein expression. Conclusively, AMPK overexpression could partially rescue the PD flies via improving PINK1^B9 flies' mitochondrial function.

Parkinson's disease (PD) is one of the most influential diseases in the world, and the current medication only can relieve the clinical symptoms but not slow the progression of PD. Therefore, we intend to examine the neuroprotective activity of plant-derived compound isotetrandrine (ITD) in vitro and in vivo. In vitro, cells were cotreated with ITD and LPS to detect the inflammatory-related protein and mRNA. In vivo, zebrafish were pretreated with ITD and inhibitors prior to 6-OHDA treatment. Then, the behavior was monitored at 5 dpf. Our result showed ITD inhibited LPS-induced upregulation of iNOS, COX-2 protein expression, and iL-6, inos, cox-2, and cd11b mRNA expression in BV2 cells. The data in zebrafish also demonstrated a significant improvement of ITD on the 6-OHDA-induced locomotor deficiency. ITD also improved 6-OHDA-induced apoptosis in zebrafish PD. We also pharmacologically validated the mechanism with three inhibitors, including LY294002, PI3K inhibitor; LY32141996, ERK inhibitor, SnPP, and HO-1 inhibitors. All of these inhibitors could abolish the neuroprotective effect of ITD partially in locomotor activity. Besides, the molecular level also showed the same trend. Treatment of these inhibitors could significantly abolish ITD-induced antineuroinflammatory and antioxidative stress effects in zebrafish PD. Our study showed ITD possessed a neuroprotective activity in zebrafish PD. The mRNA level also supported our arguments. The neuroprotection of ITD might be through antineuroinflammation and antiapoptosis pathways via PI3K, ERK, and HO-1.