Intestinal dysfunction in Parkinson's disease: Lessons learned from translational studies and experimental models

2016 ◽  
Vol 28 (12) ◽  
pp. 1781-1791 ◽  
Author(s):  
C. Pellegrini ◽  
R. Colucci ◽  
L. Antonioli ◽  
E. Barocelli ◽  
V. Ballabeni ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Experimental Models ◽  
Lessons Learned ◽  
Translational Studies

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 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 The role of dopamine in the brain - lessons learned from Parkinson's disease

NeuroImage ◽  
2019 ◽  
Vol 190 ◽  
pp. 79-93 ◽  
Author(s):  
David Meder ◽  
Damian Marc Herz ◽  
James Benedict Rowe ◽  
Stéphane Lehéricy ◽  
Hartwig Roman Siebner
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Lessons Learned ◽  
The Brain

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.

Upgraded Methodology for the Development of Early Diagnosis of Parkinson’s Disease Based on Searching Blood Markers in Patients and Experimental Models

2018 ◽  
Vol 56 (5) ◽  
pp. 3437-3450 ◽  
Author(s):  
Alexander Kim ◽  
Razina Nigmatullina ◽  
Zuleikha Zalyalova ◽  
Natalia Soshnikova ◽  
Alexey Krasnov ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Early Diagnosis ◽  
Experimental Models
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