Imaging Protein Misfolding in the Brain Using β-Sheet Ligands

Neurodegenerative diseases characterized by pathological protein accumulation in cells are termed "proteinopathies." Although various protein aggregates share cross-β-sheet structures, actual conformations vary among each type of protein deposit. Recent progress in the development of radio...

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Published inFrontiers in neuroscience Vol. 12; p. 585
Main Authors Harada, Ryuichi, Okamura, Nobuyuki, Furumoto, Shozo, Yanai, Kazuhiko
Format Journal Article
LanguageEnglish
Published Switzerland Frontiers Research Foundation 21.08.2018
Frontiers Media S.A
Subjects
Binding sites
Brain
Clinical trials
Dementia
Dementia disorders
Disease
Inflammation
Lewy bodies
Ligands
Neurodegenerative diseases
Neuroimaging
Neuroscience
NMR
Nuclear magnetic resonance
Pathology
PET
Positron emission tomography
protein aggregates
Protein folding
proteinopathies
Proteins
Radioactive tracers
tau
Tau protein
β-sheet ligands
Japan
tau
protein aggregates
PET
proteinopathies
β-sheet ligands
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Summary:Neurodegenerative diseases characterized by pathological protein accumulation in cells are termed "proteinopathies." Although various protein aggregates share cross-β-sheet structures, actual conformations vary among each type of protein deposit. Recent progress in the development of radiotracers for positron emission tomography (PET) has enabled the visualization of protein aggregates in living brains. Amyloid PET tracers have been developed, and are widely used for the diagnosis of Alzheimer's disease and non-invasive assessment of amyloid burden in clinical trials of anti-dementia drugs. Furthermore, several tau PET tracers have been successfully developed and used in the clinical studies. However, recent studies have identified the presence of off-target binding of radiotracers in areas of tau deposition, suggesting that concomitant neuroinflammatory changes might affect tracer binding. In contrast to amyloid and tau PET, there are no established tracers for imaging Lewy bodies in the human brain. In this review, we describe lessons learned from the development of PET tracers and discuss the future direction of tracer development for protein misfolding diseases.
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Reviewed by: Michael D. Devous, Avid Radiopharmaceuticals, Inc., United States; Jason Eriksen, University of Houston, United States
Edited by: Gen Sobue, Nagoya University, Japan
This article was submitted to Neurodegeneration, a section of the journal Frontiers in Neuroscience
ISSN:1662-4548
1662-453X
1662-453X
DOI:10.3389/fnins.2018.00585