Efficient RT-QuIC seeding activity for α-synuclein in olfactory mucosa samples of patients with Parkinson’s disease and multiple system atrophy

Parkinson’s disease (PD) and multiple system atrophy (MSA) are caused by two distinct strains of disease-associated α-synuclein (αSynD). Recently, we have shown that olfactory mucosa (OM) samples of patients with PD and MSA can seed the aggregation of recombinant α-synuclein by means of Real-Time Quaking-Induced Conversion (αSyn_RT-QuIC). Remarkably, the biochemical and morphological properties of the final α-synuclein aggregates significantly differed between PD and MSA seeded samples. Here, these aggregates were given to neuron-like differentiated SH-SY5Y cells and distinct inflammatory responses were observed. To deepen whether the morphological features of α-synuclein aggregates were responsible for this variable SH-SY5Y inflammatory response, we generated three biochemically and morphologically distinct α-synuclein aggregates starting from recombinant α-synuclein that were used to seed αSyn_RT-QuIC reaction; the final reaction products were used to stimulate SH-SY5Y cells. Our study showed that, in contrast to OM samples of PD and MSA patients, the artificial aggregates did not transfer their distinctive features to the αSyn_RT-QuIC products and the latter induced analogous inflammatory responses in cells. Thus, the natural composition of the αSynD strains but also other specific factors in OM tissue can substantially modulate the biochemical, morphological and inflammatory features of the αSyn_RT-QuIC products.

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Cutaneous Sympathetic Vasoconstrictor Function in Multiple System Atrophy and Parkinson's Disease

Klinische Neurophysiologie ◽

10.1055/s-2004-832221 ◽

2004 ◽

Vol 35 (03) ◽

Author(s):

G Wasner ◽

P Remien ◽

C Guballa ◽

M Hirschner ◽

A Binder ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Multiple System Atrophy

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Faculty Opinions recommendation of Dopamine transporter imaging in autopsy-confirmed Parkinson's disease and multiple system atrophy.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.13932958.15726091 ◽

2012 ◽

Author(s):

Codrin Lungu ◽

Pritha Ghosh

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Multiple System Atrophy ◽

Dopamine Transporter ◽

Dopamine Transporter Imaging

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Faculty Opinions recommendation of Dopamine transporter imaging in autopsy-confirmed Parkinson's disease and multiple system atrophy.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.13932958.15389059 ◽

2012 ◽

Author(s):

Stewart Factor

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Multiple System Atrophy ◽

Dopamine Transporter ◽

Dopamine Transporter Imaging

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Dermal and cardiac autonomic fiber involvement in Parkinson's disease and multiple system atrophy

Neurobiology of Disease ◽

10.1016/j.nbd.2021.105332 ◽

2021 ◽

pp. 105332

Author(s):

Joachim Brumberg ◽

Anastasia Kuzkina ◽

Constantin Lapa ◽

Sona Mammadova ◽

Andreas Buck ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Multiple System Atrophy

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Phenotypic manifestation of α-synuclein strains derived from Parkinson’s disease and multiple system atrophy in human dopaminergic neurons

Nature Communications ◽

10.1038/s41467-021-23682-z ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Benedict Tanudjojo ◽

Samiha S. Shaikh ◽

Alexis Fenyi ◽

Luc Bousset ◽

Devika Agarwal ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Multiple System Atrophy ◽

Neuronal Death ◽

Dopaminergic Neurons ◽

De Novo ◽

Dependent Manner ◽

Human Neurons ◽

Phenotypic Manifestation ◽

Induced Aggregation

Abstractα-Synuclein is critical in the pathogenesis of Parkinson’s disease and related disorders, yet it remains unclear how its aggregation causes degeneration of human dopaminergic neurons. In this study, we induced α-synuclein aggregation in human iPSC-derived dopaminergic neurons using fibrils generated de novo or amplified in the presence of brain homogenates from Parkinson’s disease or multiple system atrophy. Increased α-synuclein monomer levels promote seeded aggregation in a dose and time-dependent manner, which is associated with a further increase in α-synuclein gene expression. Progressive neuronal death is observed with brain-amplified fibrils and reversed by reduction of intraneuronal α-synuclein abundance. We identified 56 proteins differentially interacting with aggregates triggered by brain-amplified fibrils, including evasion of Parkinson’s disease-associated deglycase DJ-1. Knockout of DJ-1 in iPSC-derived dopaminergic neurons enhance fibril-induced aggregation and neuronal death. Taken together, our results show that the toxicity of α-synuclein strains depends on aggregate burden, which is determined by monomer levels and conformation which dictates differential interactomes. Our study demonstrates how Parkinson’s disease-associated genes influence the phenotypic manifestation of strains in human neurons.

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Intraocular pressure and choroidal thickness postural changes in multiple system atrophy and Parkinson’s disease

Scientific Reports ◽

10.1038/s41598-021-88250-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Maddalena De Bernardo ◽

Giulio Salerno ◽

Marco Gioia ◽

Luigi Capasso ◽

Maria Claudia Russillo ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Intraocular Pressure ◽

Multiple System Atrophy ◽

Choroidal Thickness ◽

Corneal Thickness ◽

Standing Position ◽

Sitting Position ◽

Postural Changes ◽

Iop Measurement

AbstractTo evaluate intraocular pressure (IOP) and choroidal thickness (ChT) postural changes in multiple system atrophy (MSA), Parkinson’s disease (PD) patients and healthy controls (HC). 20 MSA patients, 21 PD patients and 14 HC, were examined. All subjects underwent a complete examination, including corneal thickness, ChT, IOP and axial length (AL) measurements. IOP measurement was performed in supine, sitting, and standing positions, whereas ChT in sitting and standing positions. Supine to standing IOP variations were significantly higher in MSA vs PD(p = 0.01) and in MSA vs HC (p < 0.0001), whereas no significant differences were observed between PD and HC (p = 0.397). Mean sub-foveal ChT in MSA was 240 ± 92 μm in sitting position, and 215 ± 94 μm in standing position with a significant reduction (p = 0.008). Mean sub-foveal ChT in PD was 258 ± 79 μm in sitting position, and 259 ± 76 μm in standing position (p = 0.887). In HC it was 244 ± 36 μm in sitting position, and 256 ± 37 μm in standing position with a significant increase (p = 0.007). The significant IOP and ChT postural changes can be considered additional hallmarks of autonomic dysfunction in MSA and further studies are needed to consider them as biomarkers in the differential diagnosis with PD.

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A Comparison of Pain between Parkinson’s Disease and Multiple System Atrophy: A Clinical Cross-Sectional Survey

Pain Research and Management ◽

10.1155/2019/3150306 ◽

2019 ◽

Vol 2019 ◽

pp. 1-6

Author(s):

He-Yang You ◽

Lei Wu ◽

Hai-Ting Yang ◽

Chen Yang ◽

Xiao-Ling Ding

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Multiple System Atrophy ◽

Rating Scale ◽

Depression Scale ◽

Healthy Controls ◽

Cross Sectional Survey ◽

Cross Sectional ◽

Disease Rating ◽

Vas Scores

Background. Pain is frequent in Parkinson’s disease (PD) and Parkinson-plus syndrome. This study aimed to assess the prevalence, characteristics, therapy (especially the effect of dopaminergic therapy), and associated symptoms of pain in Parkinson's disease and multiple system atrophy (MSA) patients. Methods. Seventy-one PD patients, sixty-five MSA patients, and forty age-matched healthy controls were enrolled and evaluated by using the German pain questionnaire and visual analogue scale (VAS). In addition, the influence of pain in PD patients on anxiety, depression, and the quality of life was assessed with the Hospital Anxiety and Depression Scale (HADS) and Parkinson’s Disease Questionnaire (PDQ-39). Results. Compared to that of the healthy controls, the PD and MSA patients had a significantly higher presence of pain (P<0.01, P<0.01). PD patients had a higher presence of pain than MSA patients (P=0.007). No difference in VAS scores was observed between the PD and MSA patients (P=0.148). A total of 21 PD patients (42.85%) with pain and 13 MSA patients (43.33%) with pain received treatment. A total of 13 PD patients with pain and 6 MSA patients with pain had an improved pain intensity after using dopaminergic medication. The differences in the disease duration, Hoehn and Yahr stages, and scores on the Unified Parkinson’s Disease Rating Scale motor score, HAD-D, HAD-A, and PDQ-39 were significant between the PD patients with and without pain. Conclusion. PD and MSA patients are prone to pain with insufficient treatment. Pain interventions should be provided as soon as possible to improve the patient’s life.

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