+ Translate
+ Most Popular
Spermatogenic and steroidogenic impairment after chromium treatment in rats
Prediction of enthalpy of formation based on refined crystal structures of multisite compounds; Part 1, Theories and examples
Intrastromal photorefractive keratectomy for myopia by Nd:YLF picosecond laser
Teachers' beliefs about the role of prior language knowledge in learning and how these influence teaching practices
Classification and genesis of submarine iron-manganese deposits
Insecta a Cl. G. N. Potanin in China et in Mongolia novissime lecta. XVII. Hemiptera-Heteroptera
On the occurrence of the splendid genus Machaerothrix Haupt in Tsushima, with some remarks on the genus (Hymenoptera, Pompilidae)
Enamel craze lines
Gynecologic examination of the child and the adolescent
Periosteal osteoclasts, skeletal development and ageing
Fibrodysplasia ossificans progressiva in a Nigerian: a case report
The chronically ill patient with anorexia nervosa development, phenomenology, and therapeutic considerations
Kummelonautilus taiwanum sp. nov. (Nautilida) from the early Miocene Shihmen Formation, Chungliao, Nantou, west-central Taiwan
Efficacy of Droncit against Dipylidium caninum in dogs
Pierids of the genus Euchloe Klots (Lepidoptera, Pieridae) from Siberia and the Far East.
C5A anaphylatoxin and its seven transmembrane-segment receptor
Failure to practice evidence-based medicine: why do physicians not treat patients with heart failure with angiotensin-converting enzyme inhibitors?
Empirical comparisons of proportional hazards regression, Poisson regression, and logistic regression in the analysis of occupational cohort data
Pollination of flowers of sweet and sour cherries
Isopodi terrestri raccolti nell' Estremo Oriente
Morphometric observations on Dipylidium caninum from dogs and cats in Austria
Chelation effectiveness of zinc proteinates demonstrated
Alopecia--a psychosomatic disease picture? I. Review of the literature
Monitoring equity in health and healthcare: a conceptual framework
Hemodynamic evaluation of the Biocor heterologous prosthesis

Sensitive fluorescence polarization technique for rapid screening of (X-Synuclein Oligomerization/Fibrillization inhibitors

Sensitive fluorescence polarization technique for rapid screening of (X-Synuclein Oligomerization/Fibrillization inhibitors

Biochemistry 46(44): 12522-12529

ISSN/ISBN: 0006-2960

Parkinson's disease (PD) is characterized by the accumulation of fibrillar alpha-synuclein (alpha-Syn) inclusions known as Lewy bodies (LBs) and Lewy neurites. Mutations in the alpha-Syn gene or extra copies thereof cause familial PD or dementia with LBs (DLB) in rare kindreds, but abnormal accumulations of wildtype alpha-Syn also are implicated in the pathogenesis of sporadic PD, the most common movement disorder. Insights into mechanisms underlying alpha-Syn mediated neurodegeneration link alpha-Syn oligomerization and fibrillization to the onset and progression of PD. Thus, inhibiting alpha-Syn oligomer or fibril formation is a compelling target for discovering disease modifying therapies for PD, DLB, and related synucleinopathies. Although amyloid dyes recognize alpha-Syn fibrils, efficient detection of soluble oligomers remains a challenge. Here, we report a novel fluorescence polarization (FP) technique for examining alpha-Syn assembly by monitoring changes in its relative molecular mass during progression of normal alpha-Syn from highly soluble monomers to higher order multimers and thence insoluble amyloid fibrils. We report that FP is more sensitive than conventional amyloid dye methods for the quantification of mature fibrils, and that FP is capable of detecting oligomeric alpha-Syn, allowing for rapid automated screening of potential inhibitors of alpha-Syn oligomerization and fibrillization. Furthermore, FP can be combined with an amyloid dye in a single assay that simultaneously provides two independent biophysical readouts for monitoring a-Syn fibrillization. Thus, this FP method holds potential to accelerate discovery of disease modifying therapies for LB PD, DLB, and related neurodegenerative synucleinopathies.

Please choose payment method:

(PDF emailed within 1 workday: $29.90)

Accession: 017012043

Download citation: RISBibTeXText

Related references

Sensitive fluorescence polarization technique for rapid screening of alpha-synuclein oligomerization/fibrillization inhibitors. Biochemistry 46(44): 12522-12529, 2007

Different Roles of Human Cytochrome P450 2C9 and 3A Enzymes in Diclofenac 4'- and 5-Hydroxylations Mediated by Metabolically Inactivated Human Hepatocytes in Previously Transplanted Chimeric Mice. Chemical research in toxicology 33(2): 634-639, 2020

Highly sensitive and selective fluorescence assays for rapid screening of endothelin-converting enzyme inhibitors. Biochemical Journal 356(Pt 3): 813-819, 2001

Acceleration of oligomerization, not fibrillization, is a shared property of both alpha-synuclein mutations linked to early-onset Parkinson's disease: implications for pathogenesis and therapy. Proceedings of the National Academy of Sciences of the United States of America 97(2): 571-576, 2000

α-Synuclein Dimers as Potent Inhibitors of Fibrillization. Journal of Medicinal Chemistry 62(22): 10342-10351, 2019

Rapid Anionic Micelle-mediated a-Synuclein Fibrillization in Vitro. The Journal of Biological Chemistry 278(47): 674-80, 2003

Rapid anionic micelle-mediated alpha-synuclein fibrillization in vitro. Journal of Biological Chemistry 278(47): 46674-46680, 2003

Dopamine and Cu+/2+ can induce oligomerization of α-synuclein in the absence of oxygen: Two types of oligomerization mechanisms for α-synuclein and related cell toxicity studies. Journal of Neuroscience Research 92(3): 359-368, 2014

Small molecule inhibitors of aggregation indicate that amyloid beta oligomerization and fibrillization pathways are independent and distinct. Journal of Biological Chemistry 282(14): 10311-10324, 2007

Fluorescence Polarization Immunoassay for Rapid, Accurate and Sensitive Determination of Ochratoxin A in Wheat. Food Analytical Methods 7(2): 298-307, 2014

Fluorescence polarization immunoassay for rapid screening of ochratoxin A in red wine. Analytical and Bioanalytical Chemistry 395(5): 1317-1323, 2009

Rapid screening of aflatoxin B1 in beer by fluorescence polarization immunoassay. Talanta 142: 170-175, 2015

Should I stay or should I go? Explaining variation in nonstate actor advocacy over time in global governance. Governance 33(2): 287-304, 2020

Fluorescence polarization immunoassay. II. Analyzer for rapid, precise measurement of fluorescence polarization with use of disposable cuvettes. Clinical Chemistry 27(7): 1198-1201, 1981

JIP test for fast fluorescence transients as a rapid and sensitive technique in assessing the effectiveness of arbuscular mycorrhizal fungi in Zea mays : Analysis of chlorophyll a fluorescence. Plant Biosystems / An International Journal Dealing with all Aspects of Plant Biology 142(2): 191-198, 2008