Process Of Parkinson's Disease Research Articles

Minimal parkinsonism in the elderly is associated with striatal dopamine loss and pontine structural damage

IntroductionTo investigate whether neurodegeneration underlying Parkinson's disease (PD) accounts for a substantial proportion of cases of minimal parkinsonism in the elderly. MethodsWe recruited 48 consecutive subjects with minimal parkinsonism who visited the clinic with cognitive complaints. All subjects did not show findings compatible with PD on 18F-FP-CIT PET scans, and had no evidence of other neurodegenerative disorders. Striatal dopamine transporter (DAT) availability was quantified, and mean diffusivity (MD) values in the pons were calculated to characterize structural damage using diffusion tensor imaging. Additionally, 35 patients with PD and 21 healthy controls were included as reference groups. ResultsIndividuals with minimal parkinsonism (mean age, 73.23 ± 7.03 years) exhibited mild decrease in DAT availability in the posterior putamen, which was at a level between that of healthy controls and patients with PD. DAT availability in the caudate and anterior putamen was also mildly decreased in the minimal parkinsonism group. Individuals with minimal parkinsonism also tended to have higher MD values in the pons compared to healthy controls. ConclusionsOur results suggest that a substantial proportion of minimal parkinsonism is associated with nigrostriatal dopamine depletion and pontine structural damage, which may be related to the disease process of prodromal PD.

Synergic control of action in levodopa-naïve Parkinson's disease patients: II. Multi-muscle synergies stabilizing vertical posture.

Postural instability is a major disabling feature in Parkinson's disease (PD). We quantified the organization of leg and trunk muscles into synergies stabilizing the center of pressure (COP) coordinate within the uncontrolled manifold hypothesis in levodopa-naïve patients with PD and age-matched control subjects. The main hypothesis was that changes in the synergic control of posture are present early in the PD process even before levodopa exposure. Eleven levodopa-naïve patients with PD and 11 healthy controls performed whole-body cyclical voluntary sway tasks and a self-initiated load-release task during standing on a force plate. Surface electromyographic activity in 13 muscles on the right side of the body was analyzed to identify muscle groups with parallel scaling of activation levels (M-modes). Data were collected both before ("off-drug") and approximately 60min after the first dose of 25/100 carbidopa/levodopa ("on-drug"). COP-stabilizing synergies were quantified for the load-release task. Levodopa-naïve patients with PD showed no COP-stabilizing synergy "off-drug", whereas controls showed posture-stabilizing multi-M-mode synergy. "On-drug", patients with PD demonstrated a significant increase in the synergy index. There were no significant drug effects on the M-mode composition, anticipatory postural adjustments, indices of motor equivalence, or indices of COP variability. The results suggest that levodopa-naïve patients with PD already show impaired posture-stabilizing multi-muscle synergies that may be used as promising behavioral biomarkers for emerging postural disorders in PD. Moreover, levodopa modified synergy metrics differently in these levodopa-naïve patients compared to a previous study of patients on chronic antiparkinsonian medications (Falaki et al. in J Electromyogr Kinesiol 33:20-26, 2017a), suggesting different neurocircuitry involvement.

The S-nitrosylation of parkin attenuated the ubiquitination of divalent metal transporter 1 in MPP+-treated SH-SY5Y cells

Abnormal iron accumulation caused by elevated levels of divalent metal transporter 1 (DMT1) contributes to progressive neurodegeneration in Parkinson's disease (PD). Parkin is a E3 ubiquitin ligase for the ubiquitination of DMT1. S-nitrosylated parkin (SNO-parkin) is commonly observed in PD. However, the effects of S-nitrosylation on the E3 ubiquitin ligase activity of parkin for the ubiquitination of DMT1 in PD are largely unknown. To elucidate the role of S-nitrosylated parkin and DMT1 in PD, SH-SY5Y cells were transfected with parkin, being treated with S-nitrosoglutathione (GSNO) and 1-methyl-4-phenylpyridinium (MPP+). The results showed increased levels of oxidized nitric oxide (NO) and S-nitrosylated parkin after the treatment of GSNO and MPP+ in parkin-transfected cells. Consistently, increased levels of DMT1, iron uptake and cell viability were observed. Interestingly, inhibition of S-nitrosylated parkin reduced the level of DMT1. Further, S-nitrosylation of parkin significantly inhibited the ubiquitination of DMT1. When HEK293T cells were transfected with plasmid of parkin with single site mutation (Cys241A, Cys260A, Cys323A), ubiquitination of DMT1 was also inhibited. However, the cells cotransfected with plasmids containing all three mutations, GSNO treatment did not affect the ubiquitination of DMT1. The expression of SNO-parkin and DMT1 protein in substantia nigra increased significantly gradually after 2 h, 4 h and 24 h with MPTP injection. These results indicate that the S-nitrosylation of parkin inhibits its E3 ubiquitin ligase activity for the ubiquitination of DMT1, which contributes to iron accumulation and degenerative process in PD. Targeted S-nitrosylation could provide a potential therapeutic strategy against PD.

The multi-faceted role of mitochondria in the pathology of Parkinson's disease.

Mitochondria are essential for neuronal function. They produce ATP to meet energy demands, regulate homeostasis of ion levels such as calcium and regulate reactive oxygen species that cause oxidative cellular stress. Mitochondria have also been shown to regulate protein synthesis within themselves, as well as within the nucleus, and also influence synaptic plasticity. These roles are especially important for neurons, which have higher energy demands and greater susceptibility to stress. Dysfunction of mitochondria has been associated with several neurodegenerative diseases, including Parkinson's disease, Alzheimer's disease, Huntington's disease, Glaucoma and Amyotrophic Lateral Sclerosis. The focus of this review is on how and why mitochondrial function is linked to the pathology of Parkinson's disease (PD). Many of the PD-linked genetic mutations which have been identified result in dysfunctional mitochondria, through a wide-spread number of mechanisms. In this review, we describe how susceptible neurons are predisposed to be vulnerable to the toxic events that occur during the neurodegenerative process of PD, and how mitochondria are central to these pathways. We also discuss ways in which proteins linked with familial PD control mitochondrial function, both physiologically and pathologically, along with their implications in genome-wide association studies and risk assessment. Finally, we review potential strategies for disease modification through mitochondrial enhancement. Ultimately, agents capable of both improving and/or restoring mitochondrial function, either alone, or in conjunction with other disease-modifying agents may halt or slow the progression of neurodegeneration in Parkinson's disease.

Identifying a Comprehensive ceRNA Network to Reveal Novel Targets for the Pathogenesis of Parkinson's Disease.

Parkinson's disease (PD) is the second commonest progressive neurodegenerative disease worldwide. Increasing evidence reveals that non-coding RNAs play roles in the pathophysiological process of PD. The notion called competing endogenous RNAs (ceRNAs) network is used to describe the roles of non-coding RNAs. According to this theory, long non-coding RNAs (lncRNAs) act as microRNAs (miRNAs) sponges by miRNA response elements or miRNA binding sites to control the availability of endogenous miRNA for binding to their target mRNAs. This study aimed to construct a ceRNA network in PD, which might have the potential to clarify the pathogenesis of PD. We investigated differential expression (DE) lncRNAs and mRNAs in substantia nigra array data GSE7621 between PD patients and healthy controls from the Gene Expression Omnibus database. And we used starBase 2.0 and miRWalk 2.0 databases to predict miRNAs that have interactions with DElncRNAs and DEmRNAs. Based on DElncRNAs, DEmRNAs and predicted miRNAs, two ceRNA networks were constructed. The first one was based on lncRNA-miRNA interactions and miRNA-mRNA interactions that shared the same miRNAs that we predicted, on which function annotation and PPI analysis were performed to identify hub genes. Hereby the second ceRNA network was generated to explore the core section in the first ceRNA network and was validated in external datasets. As a result, we identified 31 DE lncRNAs and 1,828 DEmRNAs, and finally constructed the first ceRNA network associated with PD, including 9 lncRNAs, 18 miRNAs, and 185 mRNAs. mRNAs in the first ceRNA network focused on autophagy, DNA repair and vesicle transport, which were critical pathological processes in PD. Nineteen hub genes in the first ceRNA network identified through PPI analysis, the second ceRNA network was constructed to annotate the core part of the first one. Moreover, the core subnetwork was validated in external datasets, of which several nodes including FBXL7, PTBP2, and lncRNA NEAT1 were verified. In conclusion, a ceRNA network was constructed based on the differential expression profiles of whole substantia nigra tissues of normal and PD patients, and the network was subsequently identified which revealed its association with autophagy, DNA repair and vesicle transport. The core subnetwork of the ceRNA network was identified and validated in external data. Our findings offered novel insights into the roles of ceRNAs in the pathogenesis of PD and provided promising diagnostic biomarkers.

Future Perspectives on the Relevance of Auditory Markers in Prodromal Parkinson's Disease.

Research on auditory processing in Parkinson's disease (PD) has recently made substantial progress. At present, evidence has been found for altered auditory processing in the clinical stage of PD. The auditory alterations in PD have been demonstrated with low-cost and non-invasive assessments that are already used in routine clinical practice. Since auditory alterations have been reported early in disease progression, it would be highly relevant to investigate whether auditory markers could be provided in the prodromal stage of PD. In addition, auditory alterations in early stage PD might be modulated by dopaminergic medication. Therefore, the aim of this review is (1) to summarize the literature on auditory processing in PD with a specific focus on the early disease stages, (2) to give future perspectives on which audiological and electrophysiological measurements could be useful in the prodromal stage of PD and (3) to assess the effect of dopaminergic medication on potential auditory markers in the prodromal stage of PD.

Identifying the Mechanisms of α-Synuclein-Mediated Cytotoxicity in Parkinson’s Disease: New Insights from a Bioinformatics-Based Approach

Aim: A large body of evidence has implicated the cytotoxicity of α-synuclein in Parkinson’s disease (PD). We planned to use a bioinformatics-based approach to gain further insight into this process. Materials & methods: Using STRING version 10, we identified interacting proteins of α-synuclein. Using α-synuclein and one of these interactors involved in apoptosis as query proteins, we identified other linked proteins. We further analyzed the interactions between some of these proteins by Protein–Protein Docking using ClusPro. Results: We identified BAX as an interacting protein of α-synuclein. Interactions of α-synuclein and BAX as well as BAX and BCL2L1 were determined. Conclusion: The interaction of α-synuclein and BAX could play a crucial role in the cell death process of PD where apoptosis and mitochondrial permeability transition-driven necrosis may coexist.

Role of Long Noncoding RNAs in Parkinson's Disease: Putative Biomarkers and Therapeutic Targets.

Parkinson's disease (PD) is a neurodegenerative disease characterized by bradykinesia, rigidity, and tremor. Age is the main risk factor. Long noncoding RNAs (lncRNAs) are novel RNA molecules of more than 200 nucleotides in length. They may be involved in the regulation of many pathological processes of PD. PD has a variety of pathophysiological mechanisms, including alpha-synuclein aggregate, mitochondrial dysfunction, oxidative stress, calcium homeostasis, axonal transport, and neuroinflammation. Among these, the impacts of lncRNAs on the pathogenesis and progression of PD need to be highlighted. lncRNAs may serve as putative biomarkers and therapeutic targets for the early diagnosis of PD. This study aimed to investigate the role of lncRNAs in various pathological processes of PD and the specific lncRNAs that might be used as putative diagnostic biomarkers and therapeutic targets of PD.

Neuroinflammatory Responses and Parkinson' Disease: Pathogenic Mechanisms and Therapeutic Targets.

Parkinson's disease (PD) is the second most common age-related neurodegenerative disorders of the central nervous system, which mainly impairs the motor system. However, the pathogenic mechanisms are still unclear. Gene-environment complex interaction leads to selective dopaminergic neuron death in PD. Growing evidences supports that neuroinflammatory responses are involved in the pathogenesis of PD. This review critically discusses current studies on the inflammatory response of the pathological process of PD. The mechanisms and strategies of modifying inflammatory responses would be potential treatments for neurodegenerative diseases. Graphical abstract Activated microglia canpromote the damage ofdopaminergic neurons, which inturn aggravates the activation ofmicroglia in the process of PD. Atthe same time, microglia canactivate astrocytes throughproliferation and secretion ofinflammatory factors. The role ofastrocytes on the loss ofdopaminergic neurons is stillcontroversial in PD. (Nonsteroidalanti-inflammatory drugs,NSAIDs. adiposed-derived stemcells, ADSCs.nicotinamideadenine dinucleotide phosphate,NADPH. signal transducers andactivators of transcription,STAT.DJ-1,Aliases forPARK7.mesencephalic astrocytederivedneurotrophic factor,MANF.Ciliary neurotrophicfactor,CNTF.glial cell linederivedneurotrophic factor,GDNF.Wnt Family Member1,Wnt1). Graphical abstract Mitochondrial dysfunction causes neuroinflammation throughDAMPs and a series of factors such as oxidative stress andinflammatory bodies in PD. (Damage-associated molecular patterns,DAMPs. reactive oxygen species, ROS). Graphical abstract Various mechanismsparticipate in NLRP3 activation,causing microglia activation inPD. ( -synuclein, -syn.) TolllikeReceptor 2, TLR2. Toll-likeReceptor 4, TLR4. TumorNecrosis Factor, TNF.Apoptosisassociated speck like proteincontaining a CARD, ASC).

Identification and optimization of piperine analogues as neuroprotective agents for the treatment of Parkinson’s disease via the activation of Nrf2/keap1 pathway

Parkinson’s disease (PD) is a slowly progressive and complex neurodegenerative disorder. Up to date, there are no approved drugs that could slow or reverse the neurodegenerative process of PD. Here, we reported the synthesis of series of piperine analogues and the evaluation of their neuroprotective effects against hydrogen peroxide (H2O2) induced damage in the neuron-like PC12 cells. Among these analogues, 3b exhibited the most potent protection effect and its underlying mechanism was further investigated. Further results indicated that the ROS scavenging and cytoprotection effect of 3b might be related to the Nrf2 activation and upregulation of related phase II antioxidant enzymes, such as HO-1 and NQO1. In in vivo study, oral administration (100 mg/kg) of 3b significantly attenuated PD-associated behavioral deficits in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD and protected tyrosine hydroxylase-immunopositive dopaminergic neurons. Our results provided evidence that 3b might be a promising candidate for Parkinson’s disease treatment.

Calpain mediated expansion of CD4+ cytotoxic T cells in rodent models of Parkinson's disease

Parkinson's disease (PD), a debilitating progressive degenerative movement disorder associated with loss of dopaminergic (DA) neurons in the substantia nigra (SN), afflicts approximately one million people in the U.S., including a significant number of Veterans. Disease characteristics include tremor, rigidity, postural instability, bradykinesia, and at a cellular level, glial cell activation and Lewy body inclusions in DA neurons. The most potent medical/surgical treatments do not ultimately prevent disease progression. Therefore, new therapies must be developed to halt progression of the disease. While the mechanisms of the degenerative process in PD remain elusive, chronic inflammation, a common factor in many neurodegenerative diseases, has been implicated with associated accumulation of toxic aggregated α-synuclein in neurons. Calpain, a calcium-activated cysteine neutral protease, plays a pivotal role in SN and spinal cord degeneration in PD via its role in α-synuclein aggregation, activation/migration of microglia and T cells, and upregulation of inflammatory processes. Here we report an increased expression of a subset of CD4+ T cells in rodent models of PD, including MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) mice and DSP-4 [N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine hydrochloride]/6-hydroxydopamine rats, which produced higher levels of perforin and granzyme B - typically found in cytotoxic T cells. Importantly, the CD4+ cytotoxic subtype was attenuated following calpain inhibition in MPTP mice, suggesting that calpain and this distinct CD4+ T cell subset may have critical roles in the inflammatory process, disease progression, and neurodegeneration in PD.

Tianma Gouteng granules decreases the susceptibility of Parkinson's disease by inhibiting ALOX15-mediated lipid peroxidation

Ethnopharmacological relevanceTianma Gouteng granules (TG), a clinical prescription of traditional Chinese medicine, has been clinically applied to treat Parkinson's disease (PD) in combination with Madopar, as included in the Chinese Pharmacopoeia (2015). TG has the potential to decrease the susceptibility of PD pharmacologically, however the mechanisms need detailed demonstration. Aim of the studyTo evaluate the pharmacological activities, as well as the possible mechanism of TG in diverse models of PD. Materials and methods6-OHDA-treated rats, MPTP-treated mice, and α-synuclein A53T overexpressed mice, were utilized as PD animal models. Rotarod, locomotor activity, inclined plane and traction tests were used for behavioral assessment. Immunohistochemistry was used for tyrosine hydrolase determination. Western blot were conducted for detection of 4-HNE and 15-lipoxygenase-1 (ALOX15). The interactions of ALOX15 with the components in TG were predicted by molecular docking approach. ResultsLipid peroxidation was involved in dopaminergic neuron damage in 6-OHDA-induced rat models. In MPTP-treated mice, the inhibition of lipid peroxidation improved behavioral and pathological symptoms of PD. The lipid peroxidation-related protein, ALOX15 was found to be the key factor in PD process in diverse PD models including 6-OHDA-treated rats, MPTP-treated mice, and α-synuclein A53T overexpressed mice. TG treatment significantly relieved behavioral and pathological symptoms of MPTP-induced PD mouse models with a potential mechanism of alleviating ALOX15-induced lipid peroxidation. Moreover, the results of molecular docking analysis show that compounds in TG might have interactions with ALOX15. ConclusionsTG effectively improved the behavioral and dopaminergic neuron damage in diverse PD models. The mechanism of this action may be related to the direct inhibition of ALOX15 and the relief of lipid peroxidation.

Lanthionine ketimine ester improves outcome in an MPTP-induced mouse model of Parkinson's disease via suppressions of CRMP2 phosphorylation and microglial activation

Parkinson's disease (PD) is characterized by progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNc). Levodopa (L-Dopa), the current main treatment for PD, reduces PD symptoms by partially replacing dopamine, but it does not slow neurodegeneration. Recent studies have evidenced that neuroinflammatory processes contribute to the degeneration of dopaminergic neurons in the SNc under cytopathic conditions, while other lines of inquiry have implicated phosphorylation of collapsin response mediator protein 2 (CRMP2) as a causal factor in axonal retraction after neural injury. We recently reported on the therapeutic effect of lanthionine ketimine ester (LKE) which associates with CRMP2 following axonal injury in the spinal cord.In the present study, we report that LKE protects SNc dopaminergic neurons after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) challenge, a common model for PD, and reduces the number of activated microglia proximal to the damaged SNc. The results also show that MPTP-induced motor impairment was suppressed in LKE treatment. Furthermore, the results show that LKE inhibits the elevation of CRMP2 phosphorylation in dopaminergic neurons in the SNc after MPTP injection. These data suggest that modification of CRMP2 phosphorylation and suppression of microglial activation with LKE administration may represent a novel strategy for slowing progress of pathological processes in PD.

Recent advances in dopaminergic strategies for the treatment of Parkinson's disease.

sParkinson’s disease (PD) is the second most common progressive neurodegenerative disease worldwide. However, there is no available therapy reversing the neurodegenerative process of PD. Based on the loss of dopamine or dopaminergic dysfunction in PD patients, most of the current therapies focus on symptomatic relief to improve patient quality of life. As dopamine replacement treatment remains the most effective symptomatic pharmacotherapy for PD, herein we provide an overview of the current pharmacotherapies, summarize the clinical development status of novel dopaminergic agents, and highlight the challenge and opportunity of emerging preclinical dopaminergic approaches aimed at managing the features and progression of PD.

Impulsive-compulsive disorders in Parkinson's Disease: influence on individual and social decision-making processes

Parkinson's Disease (PD) has been considered for a long time as a neurodegenerative disorder affecting mainly motor functions, because of the involvement of basal ganglia. Recent research has shown that these brain structures have a crucial role even in higher level cognitive and social functions, as executive ones, impulse control and decision-making. A research of the peer-reviewed scientific literature was conducted in order to identify articles on the dysfunctions in individual and social decision-making in PD. This work provides the reader with a literature review on individual and social decision-making processes in PD, highlighting how the existence of impulse control disorders and the associated reward-seeking behaviors might elucidate the social symptoms of PD, both in terms of abnormal risk proneness and/or reward salience.

Studies on the Bottom-Up and Top-Down Neural Information Flow Alterations in Neurodegeneration.

A proper explanation for perceptual symptoms in neurodegenerative disorders including Alzheimer's disease and Parkinson's disease (PD) is still lacking. This study aimed at investigating the imbalance between 'bottom-up' and 'top-down' information flow (IF) and processing in PD in relation with visual hallucination symptoms. Here, we looked at bottom-up and top-down IF markers using resting state electroencephalographic (EEG) data from PD patients analyzed through three different IF measures (direct Directed Transfer Function (dDTF), full frequency Directed Transfer Function (ff-DTF), and renormalized Partial Directed Coherence (rPDC). We observed an increased gamma band IF and a reduced beta band IF in PD patients compared to healthy controls. Additionally, we noticed a reduced theta band IF in PD patients using dDTF as a measure of IF. By source localizing the EEG activity of the PD patients and healthy controls, we looked at the alterations of IF in the prefrontal cortex of PD patients as well. In line with previous studies, our results suggest that the delicate balance between bottom-up and top-down IF is disrupted in Parkinson's disease potentially contributing to the cognitive symptoms of PD patients.

The NLRP3 inflammasome as a bridge between neuro-inflammation in metabolic and neurodegenerative diseases.

Evidence increasingly suggests that type 2 diabetes mellitus (T2DM) is a risk factor for neurodegenerative diseases (NDDs), such as Alzheimer's disease (AD) and Parkinson's disease (PD). These diseases share many pathological processes, including oxidative stress, local inflammation/neuroinflammation and chronic, low-grade (systemic) inflammation, which are exacerbated by aging, a common risk factor for T2DM and NDDs. Here, we focus on the link between chronic inflammation driven by peripheral metabolic disease and how this may impact neurodegeneration in AD and PD. We review the relationship between these common pathological processes in AD and PD from the perspective of the "pro-inflammatory" signaling of the nucleotide-binding oligomerization domain (NOD)-, leucine-rich repeat- (LRR)-, and pyrin domain-containing protein 3 (NLRP3) inflammasome complex. Since the need for effective disease-modifying therapies in T2DM, AD and PD is significant, the relationship between these diseases is important as a positive clinical impact on one may benefit the others. We briefly consider how novel strategies may target neuro-inflammation and provide potential therapies for AD and PD.

Olfactory dysfunction correlates with putaminal dopamine turnover in early de novo Parkinson's disease.

Although olfactory dysfunction is one of the most well-established prodromal symptoms in Parkinson's disease (PD), its correlation with clinical disease progression or dopaminergic dysfunction still remains unclear. We here evaluated the association of striatal dopamine metabolism and olfactory function in a homogenous cohort of 30 patients with early untreated de novo PD. Striatal dopamine metabolism was assessed by the extended 18Fluorodopa PET scanning protocol to measure 18Fluorodopa uptake (Kocc) and the effective dopamine distribution volume ratio (EDVR) as the inverse of dopamine turnover. Olfactory function was estimated by the "Sniffin' Sticks" test including odor threshold (T), discrimination (D) and identification (I) assessment. We detected moderate correlations of the EDVR in the posterior putamen with the TDI composite score (r = 0.412; p = 0.024; Pearson's correlation test) and the odor identification score (r = 0.444; p = 0.014). These correlations were confirmed by multivariate regression analyses using age, sex, symptom duration and disease severity as measured by UPDRSIII motor score as candidate covariates. No other associations were observed between olfaction measures and Kocc and EDVR in all striatal regions. Together, olfactory dysfunction in early PD is not correlated with striatal 18Fluorodopa uptake as a measure for dopaminergic degeneration, but with putaminal dopamine turnover as a marker for dopaminergic presynaptic compensatory processes in early PD. These results should be treated as hypothesis generating and require confirmation by larger multicenter studies.

Activated Schwann cells and increased inflammatory cytokines IL-1β, IL-6, and TNF-α in patients' sural nerve are lack of tight relationship with specific sensory disturbances in Parkinson's disease.

AimsNeuroinflammation is one of the most important processes in the pathogenesis of Parkinson's disease (PD). Sensory disturbances are common in patients with PD, but the underlying pathophysiological mechanisms remain unknown. This study aimed to characterize the activation of Schwann cells (SCs) and the increase of expression of inflammatory cytokines IL‐1β, IL‐6, and TNF‐α in the sural nerve of PD, and further explore whether peripheral nerve inflammation is the cause of PD sensory disturbances.MethodsA total of 14 patients with PD (including 5 with sensory disturbances and 9 without sensory disturbances) and 6 controls were included. The excitation and conduction function of sural nerve was detected by sural nerve electrophysiological examination. With sural nerve biopsy samples, ultrastructural changes of sural nerve were observed by electron microscopy; Schwann cell biomarker glial fibrillary acid protein (GFAP) and inflammatory cytokines including interleukin‐1beta (IL‐1β), interleukin 6 (IL‐6), and tumor necrosis factor‐alpha (TNF‐α) were detected by immunohistochemistry, and the outcome of immunostaining slice was semiquantitatively counted; double immunofluorescence was used to identify the locus immunoreactive for inflammatory cytokines.ResultsCompared with healthy controls, nerve conduction velocity (NCV) slowed down and sensory nerve action potential (SNAP) amplitude decreased in PD patients, accompanied by axonal degeneration and demyelinating lesions, and expression of GFAP and inflammatory cytokines was increased. Inflammatory cytokines were significantly colocalized with GFAP and slightly colocalized with NF. These indicators did not differ significantly between PD patients with and without sensory disturbances.ConclusionOur study results suggest that peripheral sensory nerve injury exists in PD patients, accompanied by Schwann cell activation and inflammation, thus demonstrate peripheral nerve inflammation participates in the pathophysiological process of PD but it is not necessarily related to the patient's sensory disturbance.

The Effect of Human Umbilical Cord Mesenchymal Stromal Cells in Protection of Dopaminergic Neurons from Apoptosis by Reducing Oxidative Stress in the Early Stage of a 6-OHDA-Induced Parkinson’s Disease Model

Oxidative stress is an important cause of dopaminergic (DA) neuron apoptosis in Parkinson’s disease (PD). Mesenchymal stromal cells (MSCs) possess antioxidative features. In this study, we investigated whether MSCs could reduce oxidative stress and protect DA neurons from apoptosis by intravenous (I.V.) injection in the early stage of a 6-hydroxydopamine (6-OHDA)-induced PD model. MSCs were injected into the tail vein of mice, and behavioral tests, immunofluorescence staining, western blot, and oxidative stress levels were assessed at different time points. After 6-OHDA exposure, DA neuron apoptosis was detected, together with severe oxidative stress in brain and periphery. Compared with the non-transplanted sham controls, motor function in the 6-OHDA-lesioned group after I.V. injection of MSCs was significantly improved, and the levels of DA neuron apoptosis and oxidative stress decreased. The results demonstrate that MSCs can rescue DA neurons from ongoing apoptosis by reducing oxidative stress, and provide insights on developing new therapeutic strategies to offset the degenerative process of PD.