scholarly journals The pathophysiology of neurodegenerative disease: Disturbing the balance between phase separation and irreversible aggregation

2020 ◽  
pp. 187-223 ◽  
Author(s):  
Chelsea J. Webber ◽  
Shuwen (Eric) Lei ◽  
Benjamin Wolozin
Keyword(s):  
Phase Separation ◽  
Neurodegenerative Disease ◽  
Irreversible Aggregation

scholarly journals Small molecules for modulating protein driven liquid-liquid phase separation in treating neurodegenerative disease

2019 ◽  
Author(s):  
Richard J. Wheeler ◽  
Hyun O. Lee ◽  
Ina Poser ◽  
Arun Pal ◽  
Thom Doeleman ◽  
...  
Keyword(s):  
Phase Separation ◽  
Neurodegenerative Disease ◽  
Stress Granules ◽  
Life Time ◽  
Stress Granule ◽  
Phase Behaviour ◽  
Granule Proteins ◽  
Lateral Sclerosis ◽  
Liquid Liquid Phase Separation

AbstractAmyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with few avenues for treatment. Many proteins implicated in ALS associate with stress granules, which are examples of liquid-like compartments formed by phase separation. Aberrant phase transition of stress granules has been implicated in disease, suggesting that modulation of phase transitions could be a possible therapeutic route. Here, we combine cell-based and protein-based screens to show that lipoamide, and its related compound lipoic acid, reduce the propensity of stress granule proteins to aggregate in vitro. More significantly, they also prevented aggregation of proteins over the life time of Caenorhabditis elegans. Observations that they prevent dieback of ALS patient-derived (FUS mutant) motor neuron axons in culture and recover motor defects in Drosophila melanogaster expressing FUS mutants suggest plausibility as effective therapeutics. Our results suggest that altering phase behaviour of stress granule proteins in the cytoplasm could be a novel route to treat ALS.

Bulk standards for low-temperature biological x-ray microanalysis

1984 ◽  
Vol 42 ◽  
pp. 282-283
Author(s):  
P. Echlin ◽  
M. McKoon ◽  
E.S. Taylor ◽  
C.E. Thomas ◽  
K.L. Maloney ◽  
...  
Keyword(s):  
Phase Separation ◽  
Low Temperature ◽  
Analytical Method ◽  
Salt Solutions ◽  
Absolute Concentration ◽  
Cooling Process ◽  
X Ray ◽  
The Absolute ◽  
Analytical Procedures ◽  
Electrical Conductors

Although sections of frozen salt solutions have been used as standards for x-ray microanalysis, such solutions are less useful when analysed in the bulk form. They are poor thermal and electrical conductors and severe phase separation occurs during the cooling process. Following a suggestion by Whitecross et al we have made up a series of salt solutions containing a small amount of graphite to improve the sample conductivity. In addition, we have incorporated a polymer to ensure the formation of microcrystalline ice and a consequent homogenity of salt dispersion within the frozen matrix. The mixtures have been used to standardize the analytical procedures applied to frozen hydrated bulk specimens based on the peak/background analytical method and to measure the absolute concentration of elements in developing roots.

Phase separation in sol gel-derived ceramic films of silica-zirconia, alumina-zirconia, and titania-zirconia system

1994 ◽  
Vol 52 ◽  
pp. 646-647
Author(s):  
J. Tong ◽  
L. Eyring
Keyword(s):  
Fracture Toughness ◽  
Phase Separation ◽  
Sol Gel ◽  
Great Influence ◽  
High Strength ◽  
Chemical Durability ◽  
Separation Method ◽  
Toughening Mechanism ◽  
Ceramic Films ◽  
Zirconia Toughened Alumina

There is increasing interest in composites containing zirconia because of their high strength, fracture toughness, and its great influence on the chemical durability in glass. For the zirconia-silica system, monolithic glasses, fibers and coatings have been obtained. There is currently a great interest in designing zirconia-toughened alumina including exploration of the processing methods and the toughening mechanism.The possibility of forming nanocrystal composites by a phase separation method has been investigated in three systems: zirconia-alumina, zirconia-silica and zirconia-titania using HREM. The morphological observations initially suggest that the formation of nanocrystal composites by a phase separation method is possible in the zirconia-alumina and zirconia-silica systems, but impossible in the zirconia-titania system. The separation-produced grain size in silica-zirconia system is around 5 nm and is more uniform than that in the alumina-zirconia system in which the sizes of the small polyhedron grains are around 10 nm. In the titania-zirconia system, there is no obvious separation as was observed in die alumina-zirconia and silica-zirconia system.

Phase separation in fluid additive hard sphere mixtures?

1998 ◽  
Vol 95 (2) ◽  
pp. 131-135 ◽  
Author(s):  
DOUGLAS HENDERSON DEZSO BODA KWONG-YU CHAN
Keyword(s):  
Phase Separation ◽  
Hard Sphere

Memory Processes, Aging, Cognitive Decline, and Neurodegenerative Diseases

2006 ◽  
Vol 11 (4) ◽  
pp. 304-311 ◽  
Author(s):  
Lars-Göran Nilsson
Keyword(s):  
Cognitive Impairment ◽  
Cognitive Decline ◽  
Neurodegenerative Disease ◽  
Genetic Markers ◽  
Brain Activity ◽  
Memory Performance ◽  
Modeling And Simulations ◽  
Aging And Health ◽  
Explained Variance ◽  
Different Levels

This paper presents four domains of markers that have been found to predict later cognitive impairment and neurodegenerative disease. These four domains are (1) data patterns of memory performance, (2) cardiovascular factors, (3) genetic markers, and (4) brain activity. The critical features of each domain are illustrated with data from the longitudinal Betula Study on memory, aging, and health ( Nilsson et al., 1997 ; Nilsson et al., 2004 ). Up to now, early signs regarding these domains have been examined one by one and it has been found that they are associated with later cognitive impairment and neurodegenerative disease. However, it was also found that each marker accounts for only a very small part of the total variance, implying that single markers should not be used as predictors for cognitive decline or neurodegenerative disease. It is discussed whether modeling and simulations should be used as tools to combine markers at different levels to increase the amount of explained variance.

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