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 radiotracers fo...
Main Authors: | , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Frontiers Media S.A.
2018-08-01
|
Series: | Frontiers in Neuroscience |
Subjects: | |
Online Access: | https://www.frontiersin.org/article/10.3389/fnins.2018.00585/full |
id |
doaj-42ff5505d37c4ee9b248d89c3d7ee443 |
---|---|
record_format |
Article |
spelling |
doaj-42ff5505d37c4ee9b248d89c3d7ee4432020-11-25T00:54:32ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2018-08-011210.3389/fnins.2018.00585332121Imaging Protein Misfolding in the Brain Using β-Sheet LigandsRyuichi Harada0Nobuyuki Okamura1Shozo Furumoto2Kazuhiko Yanai3Kazuhiko Yanai4Department of Pharmacology, Tohoku University Graduate School of Medicine, Sendai, JapanDivision of Pharmacology, Tohoku Medical and Pharmaceutical University, Sendai, JapanCyclotron and Radioisotope Center, Tohoku University, Sendai, JapanDepartment of Pharmacology, Tohoku University Graduate School of Medicine, Sendai, JapanCyclotron and Radioisotope Center, Tohoku University, Sendai, JapanNeurodegenerative 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.https://www.frontiersin.org/article/10.3389/fnins.2018.00585/fullproteinopathiesprotein aggregatesβ-sheet ligandsPETtau |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Ryuichi Harada Nobuyuki Okamura Shozo Furumoto Kazuhiko Yanai Kazuhiko Yanai |
spellingShingle |
Ryuichi Harada Nobuyuki Okamura Shozo Furumoto Kazuhiko Yanai Kazuhiko Yanai Imaging Protein Misfolding in the Brain Using β-Sheet Ligands Frontiers in Neuroscience proteinopathies protein aggregates β-sheet ligands PET tau |
author_facet |
Ryuichi Harada Nobuyuki Okamura Shozo Furumoto Kazuhiko Yanai Kazuhiko Yanai |
author_sort |
Ryuichi Harada |
title |
Imaging Protein Misfolding in the Brain Using β-Sheet Ligands |
title_short |
Imaging Protein Misfolding in the Brain Using β-Sheet Ligands |
title_full |
Imaging Protein Misfolding in the Brain Using β-Sheet Ligands |
title_fullStr |
Imaging Protein Misfolding in the Brain Using β-Sheet Ligands |
title_full_unstemmed |
Imaging Protein Misfolding in the Brain Using β-Sheet Ligands |
title_sort |
imaging protein misfolding in the brain using β-sheet ligands |
publisher |
Frontiers Media S.A. |
series |
Frontiers in Neuroscience |
issn |
1662-453X |
publishDate |
2018-08-01 |
description |
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. |
topic |
proteinopathies protein aggregates β-sheet ligands PET tau |
url |
https://www.frontiersin.org/article/10.3389/fnins.2018.00585/full |
work_keys_str_mv |
AT ryuichiharada imagingproteinmisfoldinginthebrainusingbsheetligands AT nobuyukiokamura imagingproteinmisfoldinginthebrainusingbsheetligands AT shozofurumoto imagingproteinmisfoldinginthebrainusingbsheetligands AT kazuhikoyanai imagingproteinmisfoldinginthebrainusingbsheetligands AT kazuhikoyanai imagingproteinmisfoldinginthebrainusingbsheetligands |
_version_ |
1725233853510975488 |