scholarly journals The Alpha-Synuclein RT-QuIC Products Generated by the Olfactory Mucosa of Patients with Parkinson’s Disease and Multiple System Atrophy Induce Inflammatory Responses in SH-SY5Y Cells

Cells ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 87
Author(s):  
Chiara Maria Giulia De Luca ◽  
Alessandra Consonni ◽  
Federico Angelo Cazzaniga ◽  
Edoardo Bistaffa ◽  
Giuseppe Bufano ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Multiple System Atrophy ◽  
Inflammatory Responses ◽  
Alpha Synuclein ◽  
Olfactory Mucosa ◽  
Morphological Properties ◽  
Reaction Products ◽  
Distinctive Features ◽  
Specific Factors

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.

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

2019 ◽  
Vol 8 (1) ◽  
Author(s):  
Chiara Maria Giulia De Luca ◽  
Antonio Emanuele Elia ◽  
Sara Maria Portaleone ◽  
Federico Angelo Cazzaniga ◽  
Martina Rossi ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Multiple System Atrophy ◽  
Olfactory Mucosa

scholarly journals Single Cell Atlas of Human Putamen Reveals Disease Specific Changes in Synucleinopathies: Parkinson's Disease and Multiple System Atrophy

2021 ◽  
Author(s):  
Rahul Pande ◽  
Yinyin Huang ◽  
Erin Teeple ◽  
Pooja Joshi ◽  
Amilcar Flores-Morales ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Multiple System Atrophy ◽  
Single Cell ◽  
Alpha Synuclein ◽  
Cell Type ◽  
Distinct Cell Type ◽  
Altered Expression ◽  
Cell Type Specific ◽  
Disease Specific

Understanding disease biology at a cellular level from disease specific tissues is imperative for effective drug development for complex neurodegenerative diseases. We profiled 87,086 nuclei from putamen tissue of healthy controls, Parkinson's Disease (PD), and Multiple System Atrophy (MSA) subjects to construct a comprehensive single cell atlas. Although both PD and MSA are manifestations of alpha-synuclein protein aggregation, we observed that both the diseases have distinct cell-type specific changes. We see a possible expansion and activation of microglia and astrocytes in PD compared to MSA and controls. Contrary to PD microglia, we found absence of upregulated unfolded protein response in MSA microglia compared to controls. Differentially expressed genes in major cell types are enriched for genes associated with PD-GWAS loci. We found altered expression of major neurodegeneration associated genes, SNCA, MAPT, LRRK2, and APP, at cell-type resolution. We also identified disease associated gene modules using a network biology approach. Overall, this study creates an interactive atlas from synucleinopathies and provides major cell-type specific disease insights.

scholarly journals Temporal evolution of inflammation and neurodegeneration with alpha-synuclein propagation in Parkinson’s disease mouse model

2021 ◽  
Author(s):  
Thuy Thi Lai ◽  
Yun Joong Kim ◽  
Phuong Thi Nguyen ◽  
Young Ho Koh ◽  
Tinh Thi Nguyen ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Inflammatory Response ◽  
Mouse Model ◽  
Temporal Relationship ◽  
Temporal Evolution ◽  
Inflammatory Responses ◽  
Alpha Synuclein ◽  
Motor Dysfunction ◽  
Whole Brain

Abstract Alpha-synuclein (αSyn) propagation has been determined to play a key role in the pathomechanism of Parkinson’s disease (PD), but neurodegeneration and the involvement of inflammation in its pathologic progression are yet to be well understood with regard to temporal relationship. In this study, by means of PD mouse model injected with intrastriatal αSyn preformed fibril (PFF), the temporal evolution of αSyn propagation, inflammation, and neurodegeneration was explored in the perspective of the striatum and the whole brain. In the PFF-injected striatum, inflammatory responses including the microglia and astrocyte were activated at the earliest stage and reduced with time, and the phosphorylated form of αSyn accumulation increased behind it. Thereafter, the degeneration of striatal dopaminergic neurons became significant with the conspicuity of behavior phenotype. Similar pattern of forefront eruption of inflammation and following αSyn propagation was noted in the opposite striatum, which was not injected with PFF. Meanwhile, in analyzing the whole brain, inflammatory responses were determined to have activated at the earliest stage, and the soluble αSyn expression then increased concurrently. Inflammatory response decreased afterward, and the accumulation of the insoluble form of αSyn increased behind it. Our results suggested that the inflammatory response may precede the accumulation of the pathologic form of αSyn; thereafter, the neurodegeneration and motor dysfunction followed αSyn proliferation in PD mouse model. From this model, recognizing the temporal relationship between inflammation, αSyn propagation, and neurodegeneration may be helpful in establishing PD animal model and monitoring the effect of interventional therapy.

The plasma alpha-synuclein levels in patients with Parkinson’s disease and multiple system atrophy

2006 ◽  
Vol 113 (10) ◽  
pp. 1435-1439 ◽  
Author(s):  
P. H. Lee ◽  
G. Lee ◽  
H. J. Park ◽  
O. Y. Bang ◽  
I. S. Joo ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Multiple System Atrophy ◽  
Alpha Synuclein

Acting out Dreams: REM Sleep Behavior Disorder

2013 ◽  
Author(s):  
J. Eric Ahlskog
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Multiple System Atrophy ◽  
Rem Sleep ◽  
Sleep Stage ◽  
Rem Sleep Behavior Disorder ◽  
Behavior Disorder ◽  
Alpha Synuclein ◽  
Sleep Behavior ◽  
The Brain

Normal dreaming occurs during the deepest sleep states. Obviously, if experiencing a frightening dream, sleeping people could be injured if they jumped out of bed and started to run. Fortunately, the brain has a natural protective mechanism during dreaming: body paralysis. During the primary sleep stage in which dreaming occurs, the body’s muscle tone is shut off and muscles become limp. Only the eye muscles are spared, still able to move during a dream. This state in which dreaming takes place is rapid eye movement (REM) sleep. Restated, during REM sleep, a switch is thrown in the brain stem that shuts off body movement during dreaming. People with Lewy disorders of all types often lose this switch function. In other words, they can still move during the dreams of REM sleep. In the midst of a dream, they may act out by yelling, kicking, or hitting the air. This behavior is termed dream enactment behavior. When it is a recurring event it is termed REM sleep behavior disorder. REM sleep behavior disorder occurs in people with Lewy disorders—Parkinson’s disease, DLB, or PDD. It also occurs in another disorder in which alpha-synuclein is abnormally deposited in the nervous system, multiple system atrophy (MSA). Recall from Chapter 2 that alpha-synuclein is present in Lewy bodies and is thought to be a causative factor in all of these conditions. REM sleep behavior disorder may be present years or even decades before the occurrence of DLB, PDD, Parkinson’s disease, or multiple system atrophy. It is often one of the first signs of these disorders, predating most other manifestations. That does not mean that everyone who acts out their dreams will eventually develop Parkinson’s disease, DLB, or MSA. However, it does confer an increased risk. It should be noted that certain medications may provoke REM sleep behavior disorder, such as the commonly used antidepressants. Also, sleepwalking in children should not be confused with this disorder. Sleepwalking occurs in a different sleep stage and is not thought to be a forerunner of Lewy body conditions.

scholarly journals Distinctive Features of NREM Parasomnia Behaviors in Parkinson’s Disease and Multiple System Atrophy

PLoS ONE ◽  
2015 ◽  
Vol 10 (3) ◽  
pp. e0120973 ◽  
Author(s):  
Pietro-Luca Ratti ◽  
Maria Sierra-Peña ◽  
Raffaele Manni ◽  
Marion Simonetta-Moreau ◽  
Julien Bastin ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Multiple System Atrophy ◽  
Distinctive Features

scholarly journals Temporal Evolution of Inflammation and Neurodegeneration With Alpha-Synuclein Propagation in Parkinson's Disease Mouse Model

2021 ◽  
Vol 15 ◽  
Author(s):  
Thuy Thi Lai ◽  
Yun Joong Kim ◽  
Phuong Thi Nguyen ◽  
Young Ho Koh ◽  
Tinh Thi Nguyen ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Inflammatory Response ◽  
Mouse Model ◽  
Temporal Relationship ◽  
Temporal Evolution ◽  
Inflammatory Responses ◽  
Alpha Synuclein ◽  
Motor Dysfunction ◽  
Whole Brain

According to a few studies, α-synuclein (αSyn) propagation has been suggested to play a key role in the pathomechanism of Parkinson's disease (PD), but neurodegeneration and the involvement of inflammation in its pathologic progression are not well understood with regard to temporal relationship. In this study, with the help of the PD mouse model injected with intrastriatal αSyn preformed fibril (PFF), the temporal evolution of αSyn propagation, inflammation, and neurodegeneration was explored in the perspective of the striatum and the whole brain. In the PFF-injected striatum, inflammatory response cells, including microglia and astrocytes, were activated at the earliest stage and reduced with time, and the phosphorylated form of αSyn accumulation increased behind it. Afterward, the degeneration of striatal dopaminergic neurons became significant with the conspicuity of behavioral phenotype. Similar patterns of forefront eruption of inflammation and then followed by αSyn propagation were noted in the opposite striatum, which were not injured by PFF injection. In analyzing the whole brain, inflammatory responses were activated at the earliest stage, and the soluble αSyn expression increased concurrently. The inflammatory response decreased afterward, and the accumulation of the insoluble form of αSyn increased behind it. Our results suggested that the inflammatory response may precede the accumulation of the pathologic form of αSyn; thereafter, the neurodegeneration and motor dysfunction followed αSyn proliferation in the PD mouse model. From this model, recognizing the temporal relationship between inflammation, αSyn propagation, and neurodegeneration may be helpful in establishing the PD animal model and monitoring the effect of interventional therapy.

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

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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