Ultrasonication-based rapid amplification of α-synuclein aggregates in cerebrospinal fluid.

Ultrasonication-based rapid amplification of α-synuclein aggregates in cerebrospinal fluid.

Publication date: Apr 12, 2019

α-Synuclein aggregates, a key hallmark of the pathogenesis of Parkinson’s disease, can be amplified by using their seeding activity, and the evaluation of the seeding activity of cerebrospinal fluid (CSF) is reportedly useful for diagnosis. However, conventional shaking-based assays are time-consuming procedures, and the clinical significance of the diversity of seeding activity among patients remains to be clarified. Previously, we reported a high-throughput ultrasonication-induced amyloid fibrillation assay. Here, we adapted this assay to amplify and detect α-synuclein aggregates from CSF, and investigated the correlation between seeding activity and clinical indicators. We confirmed that this assay could detect α-synuclein aggregates prepared in vitro and also aggregates released from cultured cells. The seeding activity of CSF correlated with the levels of α-synuclein oligomers measured by an enzyme-linked immunosorbent assay. Moreover, the seeding activity of CSF from patients with Parkinson’s disease was higher than that of control patients. Notably, the lag time of patients with Parkinson’s disease was significantly correlated with the MIBG heart-to-mediastinum ratio. These findings showed that our ultrasonication-based assay can rapidly amplify misfolded α-synuclein and can evaluate the seeding activity of CSF.

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Concepts Keywords
Amyloid Seeding
Assay Biochemistry
Cerebrospinal Fluid Titration
Correlation Laboratory techniques
Fibrillation Assay
Mediastinum Disease
Oligomers
Parkinson
Pathogenesis
Sci
Throughput
Ultrasonication

Semantics

Type Source Name
pathway BSID Reproduction
gene UNIPROT SS18L1
gene UNIPROT SNTN
gene UNIPROT DYRK3
gene UNIPROT IK
gene UNIPROT RAB35
gene UNIPROT SH3YL1
gene UNIPROT ZBTB8OS
disease MESH dysautonomia
disease MESH hallucinations
disease MESH Neurodegenerative Disorder
disease DOID Lewy body disease
disease MESH Lewy body disease
disease DOID multiple system atrophy
disease MESH multiple system atrophy
drug DRUGBANK Iodide I-123
disease DOID striatonigral degeneration
disease MESH striatonigral degeneration
gene UNIPROT ACTA1
gene UNIPROT DUOXA1
gene UNIPROT MAPT
gene UNIPROT MBNL1
disease DOID synucleinopathy
gene UNIPROT BRD2
pathway BSID Aging
disease MESH Aging
gene UNIPROT F11R
disease DOID Parkinson disease
disease MESH Parkinson disease
gene UNIPROT BTG3
drug DRUGBANK Gelatin
drug DRUGBANK Sodium bicarbonate
gene UNIPROT KIT
gene UNIPROT MENT
drug DRUGBANK Trestolone
disease DOID dystonia
disease DOID hydrocephalus
disease MESH hydrocephalus
gene UNIPROT MAL
gene UNIPROT MRTFA
gene UNIPROT TIRAP
disease DOID myocardial infarction
disease MESH myocardial infarction
disease MESH fasting
drug DRUGBANK Iodophenyl
gene UNIPROT DHDDS
gene UNIPROT CIT
drug DRUGBANK L-Citrulline
gene UNIPROT SLC6A3
drug DRUGBANK Streptomycin
drug DRUGBANK Benzylpenicillin
gene UNIPROT FBXO8
gene UNIPROT FBRS
drug DRUGBANK L-Glutamine
drug DRUGBANK D-glucose
drug DRUGBANK Dextrose unspecified form
gene UNIPROT C2
drug DRUGBANK Nitrogen
gene UNIPROT CASP8AP2
gene UNIPROT FBN1
gene UNIPROT SDS
gene UNIPROT SBDS
drug DRUGBANK Sodium lauryl sulfate
drug DRUGBANK Tromethamine
gene UNIPROT NAA50
gene UNIPROT ISM1
disease DOID ism
disease DOID progressive supranuclear palsy
disease MESH progressive supranuclear palsy
gene UNIPROT NR1H4
gene UNIPROT ADRB2
gene UNIPROT BFAR
disease MESH visual
disease DOID REM sleep behavior disorder
disease MESH REM sleep behavior disorder
drug DRUGBANK Levodopa
gene UNIPROT ASXL1
gene UNIPROT PAFAH1B1
gene UNIPROT TET2
gene UNIPROT YWHAE
gene UNIPROT SF3B1
disease DOID MDS
disease MESH PARK4
gene UNIPROT SNCA
disease MESH familial
disease DOID dementia
disease MESH dementia
gene UNIPROT LARGE1
gene UNIPROT ARMC9
gene UNIPROT AKR1A1
drug DRUGBANK Water
disease MESH growth
gene UNIPROT TNFSF14
gene UNIPROT RXFP2
disease MESH Multiple
gene UNIPROT TNF
disease MESH dif
gene UNIPROT TNMD
gene UNIPROT CYLD
drug DRUGBANK Tretamine
gene UNIPROT CHST3
gene UNIPROT SLC35G1
gene UNIPROT NOVA2
disease MESH orthostatic hypotension
disease DOID myasthenia gravis
disease MESH myasthenia gravis
disease DOID spondylosis
disease MESH spondylosis
disease MESH myopathies
disease DOID normal pressure hydrocephalus
disease MESH normal pressure hydrocephalus
disease MESH Movement Disorder
gene UNIPROT TSPO
gene UNIPROT CHRM3
gene UNIPROT DEPP1
gene UNIPROT GOPC
disease MESH separated
disease DOID Creutzfeldt Jakob disease
disease MESH Creutzfeldt Jakob disease
gene UNIPROT CEP55
gene UNIPROT COL9A3
gene UNIPROT COMP
gene UNIPROT COL9A1
gene UNIPROT COL9A2
gene UNIPROT SCN8A
disease MESH Brain Diseases
gene UNIPROT AMH
drug DRUGBANK Dopamine
disease MESH tremor
disease MESH bradykinesia
drug DRUGBANK Coenzyme M
drug DRUGBANK Iobenguane
gene UNIPROT STMN1
disease MESH diagnosis
gene UNIPROT LAMC2
gene UNIPROT CSF2

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