Nonmotor Symptoms in Experimental Models of Parkinson's Disease

2017 ◽  
pp. 63-89 ◽  
Author(s):  
Nataliya Titova ◽  
Anthony H.V. Schapira ◽  
K Ray Chaudhuri ◽  
Mubasher A. Qamar ◽  
Elena Katunina ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Experimental Models ◽  
Nonmotor Symptoms

scholarly journals The Prion-Like Spreading of Alpha-Synuclein in Parkinson’s Disease: Update on Models and Hypotheses

2021 ◽  
Vol 22 (15) ◽  
pp. 8338
Author(s):  
Asad Jan ◽  
Nádia Pereira Gonçalves ◽  
Christian Bjerggaard Vaegter ◽  
Poul Henning Jensen ◽  
Nelson Ferreira
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Molecular Mechanisms ◽  
De Novo ◽  
Alpha Synuclein ◽  
Experimental Models ◽  
Cellular Factors ◽  
Recent Developments ◽  
Novel Targets ◽  
Presynaptic Protein

The pathological aggregation of the presynaptic protein α-synuclein (α-syn) and propagation through synaptically coupled neuroanatomical tracts is increasingly thought to underlie the pathophysiological progression of Parkinson’s disease (PD) and related synucleinopathies. Although the precise molecular mechanisms responsible for the spreading of pathological α-syn accumulation in the CNS are not fully understood, growing evidence suggests that de novo α-syn misfolding and/or neuronal internalization of aggregated α-syn facilitates conformational templating of endogenous α-syn monomers in a mechanism reminiscent of prions. A refined understanding of the biochemical and cellular factors mediating the pathological neuron-to-neuron propagation of misfolded α-syn will potentially elucidate the etiology of PD and unravel novel targets for therapeutic intervention. Here, we discuss recent developments on the hypothesis regarding trans-synaptic propagation of α-syn pathology in the context of neuronal vulnerability and highlight the potential utility of novel experimental models of synucleinopathies.

scholarly journals Drooling, Swallowing Difficulties and Health Related Quality of Life in Parkinson’s Disease Patients

2021 ◽  
Vol 18 (15) ◽  
pp. 8138
Author(s):  
Gladis Yohana Arboleda-Montealegre ◽  
Roberto Cano-de-la-Cuerda ◽  
César Fernández-de-las-Peñas ◽  
Carlos Sanchez-Camarero ◽  
Ricardo Ortega-Santiago
Keyword(s):  
Quality Of Life ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Disease Duration ◽  
Health Related Quality ◽  
Nonmotor Symptoms ◽  
Related Quality ◽  
Health Related ◽  
Swallowing Difficulties

Background: Parkinson’s disease (PD) is the most common neurodegenerative disorder associated with motor and nonmotor symptoms. Drooling, one of the nonmotor symptoms, can be present in 70–80% of patients with PD. The aim of this paper is to study the characteristics of PD patients with drooling compared to those without in terms of age, gender, disease duration, stage of the disease, swallowing difficulties, and health-related quality of life; methods: a cross-sectional study was conducted. The sample was divided into two groups: PD with drooling (n = 32) and PD without drooling (n = 30). Age, gender, disease duration and Hoehn & Yahr (H & Y) stage, Sialorrhea Clinical Scale for Parkinson’s Disease (SCS-PD), the 10-item Eating Assessment Tool (EAT-10), and the 39-item Parkinson’s Disease Questionnaire (PDQ-39) were compared between groups; Results: 62 individuals with PD, 40 men and 22 women (mean age 73 ± 8 years), were included. Overall, 32 patients reported drooling, and 30 did not exhibit it. The ANCOVA found significant differences between groups for the EAT-10 score (0.83, 95% CI = 5.62–9.03; p = 0.016) and SCS-PD score (1.48, 95% CI = 0.86–6.81; p < 0.001). Analysis of the PDQ-39 scores revealed no significant differences between groups for the PDQ-39 total score (p > 0.057) and in all subscales. The inclusion of gender, age, disease duration, and H & Y as covariates did not influence the results (all p > 0.05). Conclusions: drooling is related to swallowing difficulties assessed with EAT-10 but not with health-related quality of life assessed with PDQ-39 in PD patients with drooling compared to PD patients without it. Age, gender, duration of the disease, and the H & Y state of PD patients with and without drooling seem to be similar.

scholarly journals Corticostriatal Plastic Changes in Experimental L-DOPA-Induced Dyskinesia

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Veronica Ghiglieri ◽  
Vincenza Bagetta ◽  
Valentina Pendolino ◽  
Barbara Picconi ◽  
Paolo Calabresi
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Basal Ganglia ◽  
Experimental Models ◽  
Striatal Neurons ◽  
Da Receptors ◽  
Electrophysiological Studies ◽  
Plastic Changes ◽  
Stimulation Of

In Parkinson’s disease (PD), alteration of dopamine- (DA-) dependent striatal functions and pulsatile stimulation of DA receptors caused by the discontinuous administration of levodopa (L-DOPA) lead to a complex cascade of events affecting the postsynaptic striatal neurons that might account for the appearance of L-DOPA-induced dyskinesia (LID). Experimental models of LID have been widely used and extensively characterized in rodents and electrophysiological studies provided remarkable insights into the inner mechanisms underlying L-DOPA-induced corticostriatal plastic changes. Here we provide an overview of recent findings that represent a further step into the comprehension of mechanisms underlying maladaptive changes of basal ganglia functions in response to L-DOPA and associated to development of LID.

scholarly journals Motor and Nonmotor Symptoms of Parkinson’s Disease: Antagonistic Pleiotropy Phenomena Derived from α-Synuclein Evolvability?

2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
Yoshiki Takamatsu ◽  
Masayo Fujita ◽  
Gilbert J. Ho ◽  
Ryoko Wada ◽  
Shuei Sugama ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Lewy Body ◽  
Gastrointestinal Symptoms ◽  
Lewy Bodies ◽  
Antagonistic Pleiotropy ◽  
Nonmotor Symptoms ◽  
Novel Therapy ◽  
Wide Range ◽  
Lewy Body Diseases

Lewy body diseases, such as Parkinson’s disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA), are associated with a wide range of nonmotor symptoms (NMS), including cognitive impairment, depression and anxiety, sleep disorders, gastrointestinal symptoms, and autonomic failure. The reason why such diverse and disabling NMS have not been weeded out but have persisted across evolution is unknown. As such, one possibility would be that the NMS might be somehow beneficial during development and/or reproductive stages, a possibility consistent with our recent view as to the evolvability of amyloidogenic proteins (APs) such as α-synuclein (αS) and amyloid-β (Aβ) in the brain. Based on the heterogeneity of protofibrillar AP forms in terms of structure and cytotoxicity, we recently proposed that APs might act as vehicles to deliver information regarding diverse internal and environmental stressors. Also, we defined evolvability to be an epigenetic phenomenon whereby APs are transgenerationally transmitted from parents to offspring to cope with future brain stressors in the offspring, likely benefitting the offspring. In this context, the main objective is to discuss whether NMS might be relevant to evolvability. According to this view, information regarding NMS may be transgenerationally transmitted by heterogeneous APs to offspring, preventing or attenuating the stresses related to such symptoms. On the other hand, NMS associated with Lewy body pathology might manifest through an aging-associated antagonistic pleiotropy mechanism. Given that NMS are not only specific to Lewy body diseases but also displayed in other disorders, including amyotrophic lateral sclerosis (ALS) and Huntington’s disease (HD), these conditions might share common mechanisms related to evolvability. This might give insight into novel therapy strategies based on antagonistic pleiotropy rather than on individual NMS from which to develop disease-modifying therapies.

Correlations between plasma levels of amino acids and nonmotor symptoms in Parkinson’s disease

2014 ◽  
Vol 122 (3) ◽  
pp. 411-417 ◽  
Author(s):  
Qing Tong ◽  
Qinrong Xu ◽  
Qiang Xia ◽  
Yongsheng Yuan ◽  
Li Zhang ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Amino Acids ◽  
Parkinson's Disease ◽  
Plasma Levels ◽  
Nonmotor Symptoms

scholarly journals The activities of LRRK2 and GCase are positively correlated in clinical biospecimens and experimental models of Parkinson’s disease

2021 ◽  
Author(s):  
Maria Kedariti ◽  
Emanuele Frattini ◽  
Pascale Baden ◽  
Susanna Cogo ◽  
Laura Civiero ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Kinase Activity ◽  
Experimental Models ◽  
Cellular Functions ◽  
Gene Encoding ◽  
Cellular Models ◽  
Lrrk2 Kinase ◽  
The Impact ◽  
Lrrk2 Kinase Activity

AbstractLRRK2 is a kinase involved in different cellular functions, including autophagy, endolysosomal pathways and vesicle trafficking. Mutations in LRRK2 cause autosomal dominant forms of Parkinson’s disease (PD). Heterozygous mutations in GBA1, the gene encoding the lysosomal enzyme glucocerebrosidase (GCase), are the most common genetic risk factors for PD. Moreover, GCase function is altered in idiopathic PD and in other genetic forms of the disease. Recent work suggests that LRRK2 kinase activity can regulate GCase function. However, both a positive and a negative correlation have been described. To gain insights into the impact of LRRK2 on GCase, we investigated GCase levels and activity in LRRK2 G2019S knockin mice, in clinical biospecimens from PD patients carrying this mutation and in patient-derived cellular models. In these models we found a positive correlation between the activities of LRRK2 and GCase, which was further confirmed in cell lines with genetic and pharmacological manipulation of LRRK2 kinase activity. Overall, our study indicates that LRRK2 kinase activity affects both the levels and the catalytic activity of GCase.

Sign in / Sign up

Export Citation Format

Share Document