scholarly journals On the Cluster Formation of α-Synuclein Fibrils

2021 ◽  
Vol 8 ◽  
Author(s):  
Marija Dubackic ◽  
Ilaria Idini ◽  
Veronica Lattanzi ◽  
Yun Liu ◽  
Anne Martel ◽  
...  

The dense accumulation of α-Synuclein fibrils in neurons is considered to be strongly associated with Parkinson’s disease. These intracellular inclusions, called Lewy bodies, also contain significant amounts of lipids. To better understand such accumulations, it should be important to study α-Synuclein fibril formation under conditions where the fibrils lump together, mimicking what is observed in Lewy bodies. In the present study, we have therefore investigated the overall structural arrangements of α-synuclein fibrils, formed under mildly acidic conditions, pH = 5.5, in pure buffer or in the presence of various model membrane systems, by means of small-angle neutron scattering (SANS). At this pH, α-synuclein fibrils are colloidally unstable and aggregate further into dense clusters. SANS intensities show a power law dependence on the scattering vector, q, indicating that the clusters can be described as mass fractal aggregates. The experimentally observed fractal dimension was d = 2.6 ± 0.3. We further show that this fractal dimension can be reproduced using a simple model of rigid-rod clusters. The effect of dominatingly attractive fibril-fibril interactions is discussed within the context of fibril clustering in Lewy body formation.

2021 ◽  
Vol 17 (10) ◽  
pp. e1010018
Author(s):  
Soo Jin Park ◽  
Uram Jin ◽  
Sang Myun Park

Parkinson’s disease (PD) is one of the most common neurodegenerative diseases. PD is pathologically characterized by the death of midbrain dopaminergic neurons and the accumulation of intracellular protein inclusions called Lewy bodies or Lewy neurites. The major component of Lewy bodies is α-synuclein (α-syn). Prion-like propagation of α-syn has emerged as a novel mechanism in the progression of PD. This mechanism has been investigated to reveal factors that initiate Lewy pathology with the aim of preventing further progression of PD. Here, we demonstrate that coxsackievirus B3 (CVB3) infection can induce α-syn-associated inclusion body formation in neurons which might act as a trigger for PD. The inclusion bodies contained clustered organelles, including damaged mitochondria with α-syn fibrils. α-Syn overexpression accelerated inclusion body formation and induced more concentric inclusion bodies. In CVB3-infected mice brains, α-syn aggregates were observed in the cell body of midbrain neurons. Additionally, α-syn overexpression favored CVB3 replication and related cytotoxicity. α-Syn transgenic mice had a low survival rate, enhanced CVB3 replication, and exhibited neuronal cell death, including that of dopaminergic neurons in the substantia nigra. These results may be attributed to distinct autophagy-related pathways engaged by CVB3 and α-syn. This study elucidated the mechanism of Lewy body formation and the pathogenesis of PD associated with CVB3 infection.


1994 ◽  
Vol 376 ◽  
Author(s):  
Min Y. Lin ◽  
Weili Luo ◽  
Jeffrey Lynn

ABSTRACTSmall angle neutron scattering experiments were performed on a eicosane-based ferrofluid. An average size of 88 Å can be extracted from the data, in agreement with results from electron microscopy. Below the frozen temperature of eicosane, however, the particles are seen to be in larger aggregates with a fractal dimension of 2.15, similar to those formed under reaction-limited cluster aggregation (RLCA) conditions. At high concentrations, particles form larger aggregates even in the liquid state. Applying a magnetic field introduces new structure and changes the density inside the aggregates.


1998 ◽  
Vol 543 ◽  
Author(s):  
Jian Ma ◽  
Hao Qi ◽  
Po-Zen Wong

AbstractWe report on an adsorption study on two shale samples that have previously been investigated by small-angle neutron scattering (SANS). The scattering data indicate that these samples can be characterized as surface fractals in length from 5 Å to 500 Å, with the fractal dimension D between 2.83 and 2.75. Using the existing models for adsorption on fractal surfaces, the values of D deduced from the adsorption data appear to be consistently lower than the SANS results. We discuss these findings.


2001 ◽  
Vol 15 (06n07) ◽  
pp. 912-917
Author(s):  
HISAO MORIMOTO ◽  
TORU MAEKAWA

We developed a statistical model of the cluster formation of ferromagnetic particles and analysed the cluster structures. We investigated the effect of the control parameter λ, that is, the ratio of magnetic dipole moment energy to thermal energy, and external magnetic fields on the fractal dimensions of three-dimensional ferromagnetic clusters. We found that the fractal dimension of clusters, D, changes from 5/3 to 2 as λ increases in the absence of a magnetic field. We also found that when clusters are subjected to a magnetic field, the fractal dimension decreases and the transition region from high fractal dimension to D=1 becomes shorter as λ increases.


1977 ◽  
Vol 67 (3) ◽  
pp. 1061 ◽  
Author(s):  
R. E. Boehm ◽  
D. E. Martire
Keyword(s):  

1996 ◽  
Vol 464 ◽  
Author(s):  
A.G. Qkunev ◽  
Yu.I. Aristov

ABSTRACTHere we present experimental results on adsorption of fatty acids, aliphatic alcohols, and acetone on the mesoporous silica gels with various porosity. Conclusion has been drawn that fractal resolution analysis of the silica surface may lead to apparent values of the surface dimension. These data are suggested to be analyzed by a simple model taking into account adsorbed layer thickness and steric difficulties of monolayer formation in narrow pores.


2014 ◽  
Vol 215 ◽  
pp. 190-195 ◽  
Author(s):  
Tatiana A. Pisarenko ◽  
Anatoly Frolov ◽  
Galina Kraynova

We have studied the scaling evolution of the structure and magnetic properties of the melt-spun Fe70Cr15B15(Sn) alloys. The magnetic percolation cluster about the percolation threshold forms at the vitrification stage that is determined by both the kinetics of magnetic and of transport properties and the variation of fractal dimensionality. Alloying by tin of contact surface of ribbon decreases the temperature of the cluster formation. It is shown that the evolution of a fractal ordering affects the kinetics of the physical properties of the alloys. The spectra of fractal dimensionality identify the symmetry character of melt-spun alloys. Fractal dimensionDfis reduced at the increasing complexity of hierarchical system.


Materials ◽  
2019 ◽  
Vol 12 (16) ◽  
pp. 2606 ◽  
Author(s):  
Panqi Song ◽  
Xiaoqing Tu ◽  
Liangfei Bai ◽  
Guangai Sun ◽  
Qiang Tian ◽  
...  

Small angle neutron scattering (SANS) with contrast variation was used to characterize the fractal behavior and embedded porosity of micro/nano-sized 1,3,5-triamino-2,4,6-trinitrobenzene (TATB) crystallites, gauging the effects of particle sizes on the microstructural features. Scattering results reveal that the external surface of micro-sized TATB crystallites are continuous and smooth interfaces and their internal pores display a surface fractal structure (surface fractal dimension 2.15 < DS < 2.25), while the external surface of nano-sized TATB particles exhibit a surface fractal structure (surface fractal dimension 2.36 < DS < 2.55) and their internal pores show a two-level volume fractal structure (large voids consist of small voids). The voids volume fraction of nano-sized TATB particles are found increased distinctively when compared with micro-sized TATB particles on length scale between 1 nm and 100 nm. Specific surface areas are also estimated based on Porod law method, which are coincident with Brunauer-Emmett-Teller (BET) measurements. The contrast variation technique distinguishes the information of internal voids from external surface, suggesting SANS is a powerful tool for determining the microstructural features, which can be used to establish the relationship between microstructures and properties of micro/nano-energetic materials.


Biomolecules ◽  
2019 ◽  
Vol 9 (4) ◽  
pp. 119 ◽  
Author(s):  
Emily N. Cronin-Furman ◽  
Jennifer Barber-Singh ◽  
Kristen E. Bergquist ◽  
Takao Yagi ◽  
Patricia A. Trimmer

Parkinson’s disease (PD) is a neurodegenerative disorder that exhibits aberrant protein aggregation and mitochondrial dysfunction. Ndi1, the yeast mitochondrial NADH dehydrogenase (complex I) enzyme, is a single subunit, internal matrix-facing protein. Previous studies have shown that Ndi1 expression leads to improved mitochondrial function in models of complex I-mediated mitochondrial dysfunction. The trans-mitochondrial cybrid cell model of PD was created by fusing mitochondrial DNA-depleted SH-SY5Y cells with platelets from a sporadic PD patient. PD cybrid cells reproduce the mitochondrial dysfunction observed in a patient’s brain and periphery and form intracellular, cybrid Lewy bodies comparable to Lewy bodies in PD brain. To improve mitochondrial function and alter the formation of protein aggregates, Ndi1 was expressed in PD cybrid cells and parent SH-SY5Y cells. We observed a dramatic increase in mitochondrial respiration, increased mitochondrial gene expression, and increased PGC-1α gene expression in PD cybrid cells expressing Ndi1. Total cellular aggregated protein content was decreased but Ndi1 expression was insufficient to prevent cybrid Lewy body formation. Ndi1 expression leads to improved mitochondrial function and biogenesis signaling, both processes that could improve neuron survival during disease. However, other aspects of PD pathology such as cybrid Lewy body formation were not reduced. Consequently, resolution of mitochondrial dysfunction alone may not be sufficient to overcome other aspects of PD-related cellular pathology.


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