scholarly journals Parkinson's disease, a neurodegenerative disorder that continues to be a challenge for scientific development

2021 ◽  
Vol 8 (1) ◽  
pp. 59-65
Author(s):  
Sabrina Hadjira ◽  
◽  
Bassim Bouchouf ◽  
Ahmed Menad ◽  
Souad Ameddah ◽  
...  

La maladie de Parkinson est une maladie neurodégénérative chronique associée à une perte progressive de neurones dopaminergiques dans la substance noire pars compacta et au dépôt intraneuronal d'agrégats de protéines insolubles renfermant principalement l'α-synucléine. Les mécanismes pathogènes qui se cachent derrière cette maladie restent insaisissables. Cependant, il est bien admis que les facteurs génétiques et environnementaux contribuent aux processus de la neuro-inflammation et du stress oxydatif jouant un rôle primordial dans la pathogenèse de cette maladie. Étant donné que les thérapies disponibles visent uniquement à soulager les symptômes de la maladie de Parkinson, les scientifiques visent à exploiter la compréhension des processus impliqués dans cette maladie dans le développement de nouvelles pistes pour mieux contrôler sa progression. Mots-clés : La maladie de parkinson, dopamine, stress oxydant.

2020 ◽  
Author(s):  
Depanjan Sarkar ◽  
Drupad Trivedi ◽  
Eleanor Sinclair ◽  
Sze Hway Lim ◽  
Caitlin Walton-Doyle ◽  
...  

Parkinson’s disease (PD) is the second most common neurodegenerative disorder for which identification of robust biomarkers to complement clinical PD diagnosis would accelerate treatment options and help to stratify disease progression. Here we demonstrate the use of paper spray ionisation coupled with ion mobility mass spectrometry (PSI IM-MS) to determine diagnostic molecular features of PD in sebum. PSI IM-MS was performed directly from skin swabs, collected from 34 people with PD and 30 matched control subjects as a training set and a further 91 samples from 5 different collection sites as a validation set. PSI IM-MS elucidates ~ 4200 features from each individual and we report two classes of lipids (namely phosphatidylcholine and cardiolipin) that differ significantly in the sebum of people with PD. Putative metabolite annotations are obtained using tandem mass spectrometry experiments combined with accurate mass measurements. Sample preparation and PSI IM-MS analysis and diagnosis can be performed ~5 minutes per sample offering a new route to for rapid and inexpensive confirmatory diagnosis of this disease.


2019 ◽  
pp. 158-173

Background: Parkinson’s disease (PD) is a progressive neurodegenerative disorder caused by a dopamine deficiency that presents with motor symptoms. Visual disorders can occur concomitantly but are frequently overlooked. Deep brain stimulation (DBS) has been an effective treatment to improve tremors, stiffness and overall mobility, but little is known about its effects on the visual system. Case Report: A 75-year-old Caucasian male with PD presented with longstanding binocular diplopia. On baseline examination, the best-corrected visual acuity was 20/25 in each eye. On observation, he had noticeable tremors with an unsteady gait. Distance alternating cover test showed exophoria with a right hyperphoria. Near alternating cover test revealed a significantly larger exophoria accompanied by a reduced near point of convergence. Additional testing with a 24-2 Humphrey visual field and optical coherence tomography (OCT) of the nerve and macula were unremarkable. The patient underwent DBS implantation five weeks after initial examination, and the device was activated four weeks thereafter. At follow up, the patient still complained of intermittent diplopia. There was no significant change in the manifest refraction or prism correction. On observation, the patient had remarkably improved tremors with a steady gait. All parameters measured were unchanged. The patient was evaluated again seven months after device activation. Although vergence ranges at all distances were improved, the patient was still symptomatic for intermittent diplopia. OCT scans of the optic nerve showed borderline but symmetric thinning in each eye. All other parameters measured were unchanged. Conclusion: The case found no significant changes on ophthalmic examination after DBS implantation and activation in a patient with PD. To the best of the authors’ knowledge, there are no other cases in the literature that investigated the effects of DBS on the visual system pathway in a patient with PD before and after DBS implantation and activation.


2019 ◽  
Vol 26 (20) ◽  
pp. 3719-3753 ◽  
Author(s):  
Natasa Kustrimovic ◽  
Franca Marino ◽  
Marco Cosentino

:Parkinson’s disease (PD) is the second most common neurodegenerative disorder among elderly population, characterized by the progressive degeneration of dopaminergic neurons in the midbrain. To date, exact cause remains unknown and the mechanism of neurons death uncertain. It is typically considered as a disease of central nervous system (CNS). Nevertheless, numerous evidence has been accumulated in several past years testifying undoubtedly about the principal role of neuroinflammation in progression of PD. Neuroinflammation is mainly associated with presence of activated microglia in brain and elevated levels of cytokine levels in CNS. Nevertheless, active participation of immune system as well has been noted, such as, elevated levels of cytokine levels in blood, the presence of auto antibodies, and the infiltration of T cell in CNS. Moreover, infiltration and reactivation of those T cells could exacerbate neuroinflammation to greater neurotoxic levels. Hence, peripheral inflammation is able to prime microglia into pro-inflammatory phenotype, which can trigger stronger response in CNS further perpetuating the on-going neurodegenerative process.:In the present review, the interplay between neuroinflammation and the peripheral immune response in the pathobiology of PD will be discussed. First of all, an overview of regulation of microglial activation and neuroinflammation is summarized and discussed. Afterwards, we try to collectively analyze changes that occurs in peripheral immune system of PD patients, suggesting that these peripheral immune challenges can exacerbate the process of neuroinflammation and hence the symptoms of the disease. In the end, we summarize some of proposed immunotherapies for treatment of PD.


2020 ◽  
Vol 26 (37) ◽  
pp. 4738-4746
Author(s):  
Mohan K. Ghanta ◽  
P. Elango ◽  
Bhaskar L. V. K. S.

Parkinson’s disease is a progressive neurodegenerative disorder of dopaminergic striatal neurons in basal ganglia. Treatment of Parkinson’s disease (PD) through dopamine replacement strategies may provide improvement in early stages and this treatment response is related to dopaminergic neuronal mass which decreases in advanced stages. This treatment failure was revealed by many studies and levodopa treatment became ineffective or toxic in chronic stages of PD. Early diagnosis and neuroprotective agents may be a suitable approach for the treatment of PD. The essentials required for early diagnosis are biomarkers. Characterising the striatal neurons, understanding the status of dopaminergic pathways in different PD stages may reveal the effects of the drugs used in the treatment. This review updates on characterisation of striatal neurons, electrophysiology of dopaminergic pathways in PD, biomarkers of PD, approaches for success of neuroprotective agents in clinical trials. The literature was collected from the articles in database of PubMed, MedLine and other available literature resources.


2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Xiao-yi Kuai ◽  
Xiao-han Yao ◽  
Li-juan Xu ◽  
Yu-qing Zhou ◽  
Li-ping Zhang ◽  
...  

AbstractParkinson’s disease (PD) is a neurodegenerative disorder and 70–80% of PD patients suffer from gastrointestinal dysfunction such as constipation. We aimed to assess the efficacy and safety of fecal microbiota transplantation (FMT) for treating PD related to gastrointestinal dysfunction. We conducted a prospective, single- study. Eleven patients with PD received FMT. Fecal samples were collected before and after FMT and subjected to 16S ribosomal DNA (rDNA) gene sequencing. Hoehn-Yahr (H-Y) grade, Unified Parkinson's Disease Rating Scale (UPDRS) score, and the Non-Motion Symptom Questionnaire (NMSS) were used to assess improvements in motor and non-motor symptoms. PAC-QOL score and Wexner constipation score were used to assess the patient's constipation symptoms. All patients were tested by the small intestine breath hydrogen test, performed before and after FMT. Community richness (chao) and microbial structure in before-FMT PD patients were significantly different from the after-FMT. We observed an increased abundance of Blautia and Prevotella in PD patients after FMT, while the abundance of Bacteroidetes decreased dramatically. After FMT, the H-Y grade, UPDRS, and NMSS of PD patients decreased significantly. Through the lactulose H2 breath test, the intestinal bacterial overgrowth (SIBO) in PD patients returned to normal. The PAC-QOL score and Wexner constipation score in after-FMT patients decreased significantly. Our study profiles specific characteristics and microbial dysbiosis in the gut of PD patients. FMT might be a therapeutic potential for reconstructing the gut microbiota of PD patients and improving their motor and non-motor symptoms.


2021 ◽  
pp. 1-9
Author(s):  
Kim E. Hawkins ◽  
Elodie Chiarovano ◽  
Serene S. Paul ◽  
Ann M Burgess ◽  
Hamish G. MacDougall ◽  
...  

BACKGROUND: Parkinson’s disease (PD) is a common multi-system neurodegenerative disorder with possible vestibular system dysfunction, but prior vestibular function test findings are equivocal. OBJECTIVE: To report and compare vestibulo-ocular reflex (VOR) gain as measured by the video head impulse test (vHIT) in participants with PD, including tremor dominant and postural instability/gait dysfunction phenotypes, with healthy controls (HC). METHODS: Forty participants with PD and 40 age- and gender-matched HC had their vestibular function assessed. Lateral and vertical semicircular canal VOR gains were measured with vHIT. VOR canal gains between PD participants and HC were compared with independent samples t-tests. Two distinct PD phenotypes were compared to HC using Tukey’s ANOVA. The relationship of VOR gain with PD duration, phenotype, severity and age were investigated using logistic regression. RESULTS: There were no significant differences between groups in vHIT VOR gain for lateral or vertical canals. There was no evidence of an effect of PD severity, phenotype or age on VOR gains in the PD group. CONCLUSION: The impulsive angular VOR pathways are not significantly affected by the pathophysiological changes associated with mild to moderate PD.


2021 ◽  
pp. 1-15
Author(s):  
Zijuan Zhang ◽  
Li Hao ◽  
Ming Shi ◽  
Ziyang Yu ◽  
Simai Shao ◽  
...  

Background: Glucagon-like peptide 2 (GLP-2) is a peptide hormone derived from the proglucagon gene expressed in the intestines, pancreas and brain. Some previous studies showed that GLP-2 improved aging and Alzheimer’s disease related memory impairments. Parkinson’s disease (PD) is a progressive neurodegenerative disorder, and to date, there is no particular medicine reversed PD symptoms effectively. Objective: The aim of this study was to evaluate neuroprotective effects of a GLP-2 analogue in the 1-Methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) PD mouse model. Methods: In the present study, the protease resistant Gly(2)-GLP-2 (50 nmol/kg ip.) analogue has been tested for 14 days by behavioral assessment, transmission electron microscope, immunofluorescence histochemistry, enzyme-linked immunosorbent assay and western blot in an acute PD mouse model induced by MPTP. For comparison, the incretin receptor dual agonist DA5-CH was tested in a separate group. Results: The GLP-2 analogue treatment improved the locomotor and exploratory activity of mice, and improved bradykinesia and movement imbalance of mice. Gly(2)-GLP-2 treatment also protected dopaminergic neurons and restored tyrosine hydroxylase expression levels in the substantia nigra. Gly(2)-GLP-2 furthermore reduced the inflammation response as seen in lower microglia activation, and decreased NLRP3 and interleukin-1β pro-inflammatory cytokine expression levels. In addition, the GLP-2 analogue improved MPTP-induced mitochondrial dysfunction in the substantia nigra. The protective effects were comparable to those of the dual agonist DA5-CH. Conclusion: The present results demonstrate that Gly(2)-GLP-2 can attenuate NLRP3 inflammasome-mediated inflammation and mitochondrial damage in the substantia nigra induced by MPTP, and Gly(2)-GLP-2 shows neuroprotective effects in this PD animal model.


Medicina ◽  
2021 ◽  
Vol 57 (4) ◽  
pp. 314
Author(s):  
Aida Arroyo-Ferrer ◽  
Francisco José Sánchez-Cuesta ◽  
Yeray González-Zamorano ◽  
María Dolores del Castillo ◽  
Carolina Sastre-Barrios ◽  
...  

Background: Parkinson’s disease (PD) is the second most common neurodegenerative disorder. This disease is characterized by motor symptoms, such as bradykinesia, tremor, and rigidity. Although balance impairment is characteristic of advanced stages, it can be present with less intensity since the beginning of the disease. Approximately 60% of PD patients fall once a year and 40% recurrently. On the other hand, cognitive symptoms affect up to 20% of patients with PD in early stages and can even precede the onset of motor symptoms. There are cognitive requirements for balance and can be challenged when attention is diverted or reduced, linking a worse balance and a higher probability of falls with a slower cognitive processing speed and attentional problems. Cognitive rehabilitation of attention and processing speed can lead to an improvement in postural stability in patients with Parkinson’s. Methods: We present a parallel and controlled randomized clinical trial (RCT) to assess the impact on balance of a protocol based on cognitive rehabilitation focused on sustained attention through the NeuronUP platform (Neuronup SI, La Rioja, Spain) in patients with PD. For 4 weeks, patients in the experimental group will receive cognitive therapy three days a week while the control group will not receive any therapy. The protocol has been registered at trials.gov NCT04730466. Conclusions: Cognitive therapy efficacy on balance improvement may open the possibility of new rehabilitation strategies for prevention of falls in PD, reducing morbidity, and saving costs to the health care system.


2016 ◽  
Vol 46 (4) ◽  
pp. 292-300 ◽  
Author(s):  
Lauren Hirsch ◽  
Nathalie Jette ◽  
Alexandra Frolkis ◽  
Thomas Steeves ◽  
Tamara Pringsheim

Background: Parkinson's disease (PD) is a common neurodegenerative disorder. Epidemiological studies on the incidence of PD are important to better understand the risk factors for PD and determine the condition's natural history. Objective: This systematic review and meta-analysis examine the incidence of PD and its variation by age and gender. Methods: We searched MEDLINE and EMBASE for epidemiologic studies of PD from 2001 to 2014, as a previously published systematic review included studies published until 2001. Data were analyzed separately for age group and gender, and meta-regression was used to determine whether a significant difference was present between groups. Results: Twenty-seven studies were included in the analysis. Meta-analysis of international studies showed rising incidence with age in both men and women. Significant heterogeneity was observed in the 80+ group, which may be explained by methodological differences between studies. While males had a higher incidence of PD in all age groups, this difference was only statistically significant for those in the age range 60-69 and 70-79 (p < 0.05). Conclusion: PD incidence generally increases with age, although it may stabilize in those who are 80+.


2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Elizabeth Romero-Gutiérrez ◽  
Paola Vázquez-Cárdenas ◽  
Hortensia Moreno-Macías ◽  
José Salas-Pacheco ◽  
Teresa Tusié-Luna ◽  
...  

AbstractParkinson’s disease (PD), a common neurodegenerative disorder, has a complex etiology where environmental and genetic factors intervene. While a number of genes and variants have been identified in recent decades as causative or protective agents of this condition, a limited number of studies have been conducted in mixed populations, such as Mexican Mestizos. The historical convergence of two founding groups and three ethnicities, and the increasing north-to-south gradient of Native American ancestry in Mexico resulted in a subpopulation structure with considerable genetic diversity. In this work, we investigate the influence of 21 known susceptibility variants for PD. Our case–control study, with a cohort of 311 Mexican Mestizo subjects, found a significant risk association for the variant rs1491942 in LRRK2. However, when stratification by ancestry was performed, a risk effect for MTHFR rs1801133 was observed only in the group with the highest percentage of European ancestry, and the PD risk effect for LRRK2 rs1491942 was significant in subjects with a higher ratio of Native American ancestry. Meta-analyses of these SNP revealed the effect of LRRK2 rs1491942 to be even more significant than previously described in populations of European descent. Although corroboration is necessary, our findings suggest that polymorphism rs1491942 may be useful as a risk marker of PD in Mexican Mestizos with greater Native American ancestry. The absence of associations with the remaining known risk factors is, in itself, a relevant finding and invites further research into the shared risk factors’ role in the pathophysiological mechanisms of this neurodegenerative disorder.


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