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A high-affinity fluorescence probe for copper(II) ions and its application in fluorescence lifetime correlation spectroscopy
摘要： Copper is one of the most important transition metals in many organisms where it catalyzes a manifold of different processes. As a result of copper’s redox activity, organisms have to avoid unbound ions, and a dysfunctional copper homeostasis may lead to multifarious pathological processes in cells with very severe ramifications for the affected organisms. In many neurodegenerative diseases, however, the exact role of copper ions is still not completely clarified. In this work, a high-affinity and highly selective copper probe molecule, based on the naturally occurring tetrapeptide DAHK is synthesized. The sensor (log KD = ? 12.8 ± 0.1) is tagged with a fluorescent BODIPY dye whose fluorescence lifetime distinctly decreases from 5.8 ns ± 0.2 ns to 0.4 ns ± 0.1 ns on binding to copper(II) cations. It is shown by using fluorescence lifetime correlation spectroscopy that the concentration of both probe and probe-copper complex can be simultaneously measured even at nanomolar concentration levels. This work presents a possible starting point for a new type of probe and method for future in vivo studies to further reveal the exact role of copper ions in organisms.
关键词： BODIPY,Single molecule detection,FLIM,Alzheimer,ATCUN motif,Parkinson,DAHK
更新于2025-11-21 11:24:58
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Pre-conditioning with Remote Photobiomodulation Modulates the Brain Transcriptome and Protects Against MPTP Insult in Mice
摘要： Transcranial photobiomodulation (PBM), which involves the application of low-intensity red to near-infrared light (600-1100nm) to the head, provides neuroprotection in animal models of various neurodegenerative diseases. However, the absorption of light energy by the human scalp and skull may limit the utility of transcranial PBM in clinical contexts. We have previously shown that targeting light at peripheral tissues (i.e. “remote PBM”) also provides protection of the brain in an MPTP mouse model of Parkinson’s disease, suggesting remote PBM might be a viable alternative strategy for overcoming penetration issues associated with transcranial PBM. This present study aimed to determine an effective pre-conditioning regimen of remote PBM for inducing neuroprotection and elucidate the molecular mechanisms by which remote PBM enhances the resilience of brain tissue. Balb/c mice were irradiated with 670nm light (4J/cm2 per day) targeting dorsum and hindlimbs for 2, 5 or 10 days, followed by injection of the parkinsonian neurotoxin MPTP (50mg/kg) over two consecutive days. Despite no direct irradiation of the head, 10 days of pre-conditioning with remote PBM significantly attenuated MPTP-induced loss of midbrain tyrosine hydroxylase-positive dopaminergic cells and mitigated the increase in FOS-positive neurons in the caudate-putamen complex. Interrogation of the midbrain transcriptome by RNA microarray and pathway enrichment analysis suggested upregulation of cell signaling and migration (including CXCR4+ stem cell and adipocytokine signaling), oxidative stress response pathways and modulation of the blood-brain barrier following remote PBM. These findings establish remote PBM preconditioning as a viable neuroprotective intervention and provide insights into the mechanisms underlying this phenomenon.
关键词： MPTP,microarray,Parkinson’s disease,mouse model,neuroprotection,photobiomodulation
更新于2025-09-23 15:23:52
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A Pilot Study of F-18 FP-CIT PET Imaging in Early-onset Patients with Parkinson’s Disease: Parkin versus Non-parkin Mutation
摘要： Striatal dopaminergic dysfunction in early-onset Parkinson’s disease (PD) remains to be further elucidated. Thus, as a preliminary study, we aimed to investigate detailed patterns of dopaminergic depletion in five early-onset PD patients with dynamic N-(3-[(18) F]fluoropropyl)-2-carbomethoxy-3-(4-iodophenyl) nortropane (FP-CIT) positron emission tomography (PET) scans. Two patients with parkin mutation showed more symmetric decrease of dopamine transporter (DAT) density in the putamen, whereas others displayed asymmetric reduction of DAT density in the putamen. Notably, only those with parkin mutation revealed more severe dopaminergic deficits in the anteroventral putamen rather than the posterodoral putamen. Our observation suggests, among PD patients, patients with parkin mutation may exhibit the different pattern of striatal dopaminergic depletion.
关键词： Parkinson’s Disease,Parkin Mutation,Early-Onset,Dopamine Depletion
更新于2025-09-23 15:23:52
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Different effects of alpha-Synuclein mutants on lipid binding and aggregation detected by single molecule fluorescence spectroscopy and ThT fluorescence-based measurements
摘要： Six alpha-Synuclein point mutations are currently known to be associated with familial parkinsonism: A30P, E46K, H50Q, G51D, A53E and A53T. We performed a comprehensive in vitro analysis to study the impact of all aSyn mutations on lipid binding and aggregation behavior. Markedly reduced lipid binding of A30P, moderately attenuated binding of G51D and only very slightly reduced binding for the other mutants were observed. A30P was particularly prone to form metal ion induced oligomers, whereas A53T exhibited only weak tendencies to form oligomers. In turn, fibril formation occurred rapidly in H50Q, G51D and A53T, but only slowly in A30P, suggesting mutants prone to form oligomers tend to form fibrils to a lesser extent. This was supported by the observation that fibril formation of wild type aSyn, A30P and A53T was impaired in the presence of ferric iron. Additionally, we found the aggregation kinetics of mixtures of A30P or A53T and wt aSyn to be determined by the faster aggregating aSyn variant. Our results implicate differential mechanisms playing a role in aSyn pathology on the molecular level. This might contribute to a better understanding of Parkinson′s disease pathogenesis and provide potential links to develop prevention strategies and disease-modifying therapy.
关键词： synucleinopathy,Alpha-synuclein (α‐Synuclein),Parkinson′s disease,protein‐lipid interaction,protein aggregation,mutant
更新于2025-09-23 15:23:52
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Optimization of Parameters for Quantitative Analysis of <sup>123</sup> I-ioflupane SPECT Images for Monitoring of Progression of Parkinson's Disease
摘要： Objectives: Quantitative assessment of dopamine transporter (DAT) imaging can aid in diagnosing Parkinson’s disease (PD) and assessing disease progression in the context of therapeutic trials. Previously, the software program SBRquant was applied to 123I-ioflupane SPECT images acquired on healthy controls and subjects with PD. Earlier work on optimization of the parameters for differentiating between controls and subjects with dopaminergic deficits is extended here for maximizing change measurements associated with disease progression on longitudinally acquired scans. Methods: Serial 123I-ioflupane SPECT imaging for 51 subjects with PD (conducted approximately 1 year apart) were downloaded from the Parkinson’s Progression Markers Initiative database. The software program SBRquant calculates the Striatal Binding Ratio (SBR) separately for the left and right caudate and putamen regions of interest (ROI). Parameters were varied to evaluate the number of summed transverse slices and the positioning of the striatal ROIs for determining signal to noise associated with their annual rate of change in SBR. The parameters yielding the largest change of the lowest putamen's SBR from scan 1 to scan 2 were determined. Results: For the change from scan 1 to scan 2 in the 51 subjects, the largest annual change was observed when the putamen ROI was placed 3 pixels away from the caudate and by summing 5 central striatal slices. This resulted in an 11.2 ± 4.3% annual decrease in the lowest putamen's SBR for the group. Conclusions: Quantitative assessment of DAT imaging for assessing progression of PD requires specific, optimal parameters different than those for diagnostic accuracy.
关键词： Parkinson's Disease,Dopamine Transporter Imaging,Disease Progression,Quantitative Analysis,123I-ioflupane SPECT
更新于2025-09-23 15:21:21
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[IEEE 2019 International Symposium on Ocean Technology (SYMPOL) - Ernakulam, India (2019.12.11-2019.12.13)] 2019 International Symposium on Ocean Technology (SYMPOL) - Performance Analysis of Underwater Wireless Optical Communication in terms of Received Optical Power
摘要： This paper presents a wearable inertial measurement system and its associated spatiotemporal gait analysis algorithm to obtain quantitative measurements and explore clinical indicators from the spatiotemporal gait patterns for patients with stroke or Parkinson’s disease. The wearable system is composed of a microcontroller, a triaxial accelerometer, a triaxial gyroscope, and an RF wireless transmission module. The spatiotemporal gait analysis algorithm, consisting of procedures of inertial signal acquisition, signal preprocessing, gait phase detection, and ankle range of motion estimation, has been developed for extracting gait features from accelerations and angular velocities. In order to estimate accurate ankle range of motion, we have integrated accelerations and angular velocities into a complementary filter for reducing the accumulation of integration error of inertial signals. All 24 participants mounted the system on their foot to walk along a straight line of 10 m at normal speed and their walking recordings were collected to validate the effectiveness of the proposed system and algorithm. Experimental results show that the proposed inertial measurement system with the designed spatiotemporal gait analysis algorithm is a promising tool for automatically analyzing spatiotemporal gait information, serving as clinical indicators for monitoring therapeutic efficacy for diagnosis of stroke or Parkinson’s disease.
关键词： stroke,Inertial sensing,complementary filter,Parkinson’s disease,gait analysis,sensor fusion
更新于2025-09-23 15:21:01
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Dopaminergic induction of human dental pulp stem cells by photobiomodulation: comparison of 660nm laser light and polychromatic light in the nir
摘要： Human dental pulp stem cells (hDPSCs) are able to differentiate into dopaminergic neurons and help the maintenance of partially degenerated neurons, which makes them as an alternative cell source for treatment of Parkinsons' disease (PD) patients. Here, the effect of photobiomodulation with polychromatic light source in the near infrared (NIR) range (600–1200 nm) or low level 660 nm diode laser light on hDPSCs during dopaminergic induction was investigated. Real time RT-qPCR analysis indicated that expressions of brain derived neurotrophic factor (BDNF), glial cell line derived neurotropic factor (GNDF), matrix associated protein 2 (MAP2), nuclear receptor related 1 protein (NURR1) and dopamine transporter (DAT) were increased, especially in the first 7 days of dopaminergic induction when 660 nm laser light was applied with a total energy density of 1.6 J/cm2. The activity of polychromatic light on hDPSCs depended on the differentiation media and protein type. BDNF, GDNF, NURR-1 and MAP2 expressions were increased in the presence of pre-induction factors, and decreased when the post-induction factors were added into the culture medium. In contrast with all these promising results, the dopaminergically induced hDPSCs did not show any functional characteristics of dopaminergic neurons and died after they were transferred to a new laminin coated culture plates. In conclusion, the expression of dopaminergic neuron protective protein mRNAs in hDPSCs was increased by photobiomodulation in defined conditions. However, the cells were not able to differentiate into functional dopaminergic neurons either in control or in photobiomodulated groups that are prone to cell death and exhibit immature dopaminergic neuron characteristics.
关键词： Dopaminergic neuron,Photobiomodulation,Parkinson's disease,Polychromatic light,Human dental pulp stem cells,Laser
更新于2025-09-19 17:13:59
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Positron emission tomography/computed tomography dual imaging using 18-fluorine flurodeoxyglucose and 11C-labeled 2-?2-carbomethoxy-3-?2-(4-fluorophenyl) tropane for the severity assessment of Parkinson disease
摘要： The value of dual imaging mode for the severity assessment of Parkinson disease (PD) is explored by conducting positron emission tomography computed tomography (PET/CT) double imaging using combined 18-fluorine flurodeoxyglucose (18F-FDG) brain metabolism and 11C-2b-carbomethoxy-3b-(4-fluorophenyl) tropane (11C-CFT) brain dopamine transporter (DAT). A total of 102 patients with PD and 50 healthy people in the control group are enrolled for the PET/CT dual imaging of 18F-FDG brain metabolism and 11C-CFT brain DAT. The characteristics of 18F-FDG PET/CT and 11C-CFT PET/CT imaging are analyzed by delineating the region of interest. Differences in the glucose metabolism and DAT distribution in the basal ganglia of patients with PD and healthy control group in the PET/CT imaging and the radioactive distribution characteristics of cerebral cortex in glucose metabolism imaging are compared. The characteristics of PET/CT imaging of 11C-CFT brain DAT in the ganglion region in absorbing 11C-CFT in different PD groups are analyzed. Compared with the healthy control group, changes in the cerebral glucose metabolism in the PD group mainly occur due to the increased symmetry metabolism of the nucleus of bilateral basal ganglia and the decreased metabolism of the cerebral cortex as shown in the 18F-FDG PET/CT images. With disease progression, the bilateral parietal, frontal, temporal, and occipital leaves showed different degrees of FDG metabolism. Statistically significant difference is observed for the11C-CFT absorption among the caudate nucleus and the anterior, middle, and posterior nuclei of the bilateral basal ganglia of the PD and healthy control groups. In the PD group, the bilateral caudate nucleus and the anterior, middle, and posterior parts of the putamen show decreased DAT distribution. Regardless of unilateral or bilateral symptoms, the DAT distribution in the nucleus of the contralateral basal ganglia and in the posterior part of the nucleus is substantially reduced. PET/CT dual imaging by 18F-FDG PET/CT combined with 11C-CFT PET/CT features high application value for the severity assessment of PD.
关键词： brain metabolism,dopamine transporter,computed tomography of electron emission,Parkinson disease
更新于2025-09-19 17:13:59
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[IEEE 2018 IEEE 20th International Conference on e-Health Networking, Applications and Services (Healthcom) - Ostrava, Czech Republic (2018.9.17-2018.9.20)] 2018 IEEE 20th International Conference on e-Health Networking, Applications and Services (Healthcom) - Automated Gait Analysis using a Kinect Camera and Wavelets
摘要： Studies of Parkinson’s Disease (PD) have generated particular interest in factors such as gait and posture patterns and fall risk. Human gait patterns involve a basic gait cycle that is composed of two phases: stance and swing. With gait analysis, we can derive values for spatiotemporal variables such as the walking speed, cadence, and stride length from these stance and swing phases. In this paper, we use a low-cost, quick-setup, and portable system to capture gait signals, and propose a novel method for automatically obtaining gait phases (swing and stance) using wavelets and a Kinect camera. We tested this method on six PD patients and six healthy subjects in a clinical context, finding that it could classify the gait phases with 93% accuracy, compared with clinical judgment. Such a procedure could allow clinicians to rapidly, easily, and non-invasively diagnose and assess PD patients via objective and automatic data analysis.
关键词： gait analysis,Kinect,Parkinson’s disease,gait,wavelet,swing,spatiotemporal,stance
更新于2025-09-10 09:29:36
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[EAI/Springer Innovations in Communication and Computing] Mobile Solutions and Their Usefulness in Everyday Life || Smartphone Sensing Technologies for Tailored Parkinson’s Disease Diagnosis and Monitoring
摘要： Parkinsonian syndromes are a heterogeneous entity of movement disorders, with various described subtypes. This systematic review aimed to examine the available literature on smartphone applications for assessment of Parkinson’s disease motor and nonmotor symptoms and signs. Papers published from 2013 to 2017, listed in two electronic databases—IEEE Xplore and PubMed—were searched, to identify the works related with smartphone use for PD patients’ diagnosis and monitoring. Full-text articles were analyzed to evaluate the quality of the reported methods and results, considering the validity, reliability, and sensitivity of the techniques used in the measurements as well as the Grading of Recommendations Assessment, Development and Evaluation guideline. The data from 26 full-text articles suggest that many and relevant data can be collected automatically and accurately via mobile phone. Inertial measurement units as well as capacitive, force/pressure, acoustic sensors were used for the development of smartphone-based tools to improve assessment and monitor symptoms and signs of Parkinson’s disease. Smartphone-based information on upper limbs tremor, gait, posture, balance, activities, and speech may improve quality of healthcare services for Parkinson’s disease patients and their quality of life.
关键词： diagnosis,Parkinson’s disease,motor symptoms,nonmotor symptoms,smartphone applications,monitoring
更新于2025-09-04 15:30:14