scholarly journals Protection Against Dopaminergic Neurodegeneration in Parkinson’s Disease–Model Animals by a Modulator of the Oxidized Form of DJ-1, a Wild-type of Familial Parkinson’s Disease–Linked PARK7

2011 ◽  
Vol 117 (3) ◽  
pp. 189-203 ◽  
Author(s):  
Masatoshi Inden ◽  
Yoshihisa Kitamura ◽  
Kazunori Takahashi ◽  
Kazuyuki Takata ◽  
Natsuko Ito ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Disease Model ◽  
Wild Type ◽  
Dopaminergic Neurodegeneration ◽  
Familial Parkinson’S Disease

scholarly journals Familial Parkinson's Disease Mutant E46K α-Synuclein Localizes to Membranous Structures, Forms Aggregates, and Induces Toxicity in Yeast Models

2011 ◽  
Vol 2011 ◽  
pp. 1-14 ◽  
Author(s):  
Michael Fiske ◽  
Michael White ◽  
Stephanie Valtierra ◽  
Sara Herrera ◽  
Keith Solvang ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Plasma Membrane ◽  
Mutant Form ◽  
Phospholipid Membrane ◽  
Endomembrane System ◽  
Wild Type ◽  
Significant Toxicity ◽  
Familial Parkinson’S Disease

In Parkinson’s disease (PD), midbrain dopaminergic neuronal death is linked to the accumulation of aggregated α-synuclein. The familial PD mutant form of α-synuclein, E46K, has not been thoroughly evaluated yet in an organismal model system. Here, we report that E46K resembled wild-type (WT) α-synuclein in Saccharomyces cerevisiae in that it predominantly localized to the plasma membrane, and it did not induce significant toxicity or accumulation. In contrast, in Schizosaccharomyces pombe, E46K did not associate with the plasma membrane. Instead, in one strain, it extensively aggregated in the cytoplasm and was as toxic as WT. Remarkably, in another strain, E46K extensively associated with the endomembrane system and was more toxic than WT. Our studies recapitulate and extend aggregation and phospholipid membrane association properties of E46K previously observed in vitro and cell culture. Furthermore, it supports the notion that E46K generates toxicity partly due to increased association with endomembrane systems within cells.

scholarly journals Alpha-synuclein stepwise aggregation reveals features of an early onset mutation in Parkinson’s disease

2019 ◽  
Vol 2 (1) ◽  
Author(s):  
Guilherme A. P. de Oliveira ◽  
Jerson L. Silva
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Early Onset ◽  
Point Mutations ◽  
Alpha Synuclein ◽  
Amyloid Formation ◽  
Wild Type ◽  
Cryo Electron Microscopy ◽  
Familial Parkinson’S Disease ◽  
Direct Detector

Abstract Amyloid formation is a process involving interconverting protein species and results in toxic oligomers and fibrils. Aggregated alpha-synuclein (αS) participates in neurodegenerative maladies, but a closer understanding of the early αS polymerization stages and polymorphism of heritable αS variants is sparse still. Here, we distinguished αS oligomer and protofibril interconversions in Thioflavin T polymerization reactions. The results support a hypothesis reconciling the nucleation-polymerization and nucleation-conversion-polymerization models to explain the dissimilar behaviors of wild-type and the A53T mutant. Cryo-electron microscopy with a direct detector shows the polymorphic nature of αS fibrils formed by heritable A30P, E46K, and A53T point mutations. By showing that A53T rapidly nucleates competent species, continuously elongates fibrils in the presence of increasing amounts of seeds, and overcomes wild-type surface requirements for growth, our findings place A53T with features that may explain the early onset of familial Parkinson’s disease cases bearing this mutation.

Identification of amyloidogenic proteins in the microbiomes of a rat Parkinson's disease model and wild‐type rats

2021 ◽  
Author(s):  
Line Friis Bakmann Christensen ◽  
Saeid Hadi Alijanvand ◽  
Michał Burdukiewicz ◽  
Florian‐Alexander Herbst ◽  
Henrik Kjeldal ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Disease Model ◽  
Wild Type ◽  
Amyloidogenic Proteins

scholarly journals A locomotor assay reveals deficits in heterozygous Parkinson’s disease model and proprioceptive mutants in adult Drosophila

2019 ◽  
Vol 116 (49) ◽  
pp. 24830-24839 ◽  
Author(s):  
Aman Aggarwal ◽  
Heinrich Reichert ◽  
K. VijayRaghavan
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Disease Model ◽  
Cost Effective ◽  
Fine Motor ◽  
Wild Type ◽  
Climbing Behavior ◽  
Locomotor Impairment ◽  
Locomotor Behaviors ◽  
Locomotor Disorders

Severe locomotor impairment is a common phenotype of neurodegenerative disorders such as Parkinson’s disease (PD). Drosophila models of PD, studied for more than a decade, have helped in understanding the interaction between various genetic factors, such as parkin and PINK1, in this disease. To characterize locomotor behavioral phenotypes for these genes, fly climbing assays have been widely used. While these simple current assays for locomotor defects in Drosophila mutants measure some locomotor phenotypes well, it is possible that detection of subtle changes in behavior is important to understand the manifestation of locomotor disorders. We introduce a climbing behavior assay which provides such fine-scale behavioral data and tests this proposition for the Drosophila model. We use this inexpensive, fully automated assay to quantitatively characterize the climbing behavior at high parametric resolution in 3 contexts. First, we characterize wild-type flies and uncover a hitherto unknown sexual dimorphism in climbing behavior. Second, we study climbing behavior of heterozygous mutants of genes implicated in the fly PD model and reveal previously unreported prominent locomotor defects in some of these heterozygous fly lines. Finally, we study locomotor defects in a homozygous proprioceptory mutation (Trp-γ1) known to affect fine motor control in Drosophila. Moreover, we identify aberrant geotactic behavior in Trp-γ1 mutants, thereby opening up a finer assay for geotaxis and its genetic basis. Our assay is therefore a cost-effective, general tool for measuring locomotor behaviors of wild-type and mutant flies in fine detail and can reveal subtle motor defects.

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