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Assays for the Degradation of Misfolded Proteins in Cells
Published on: August 28, 2016
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Imaging Protein Misfolding in the Brain Using β-Sheet Ligands
Ryuichi Harada1, Nobuyuki Okamura2, Shozo Furumoto3
1Department of Pharmacology, Tohoku University Graduate School of Medicine, Sendai, Japan.
Frontiers in Neuroscience
|September 7, 2018
Summary
Positron emission tomography (PET) tracers visualize protein aggregates in neurodegenerative diseases like Alzheimer's. Future research aims to develop specific PET tracers for Lewy bodies and other protein misfolding diseases.
Area of Science:
- Neuroscience
- Medical Imaging
- Biochemistry
Background:
- Proteinopathies involve pathological protein accumulation, sharing structural similarities but differing in conformation.
- Positron emission tomography (PET) enables in vivo visualization of protein aggregates in the brain.
- Amyloid and tau PET tracers are established for Alzheimer's disease diagnosis and clinical trials.
Purpose of the Study:
- To review lessons learned from PET tracer development for protein misfolding diseases.
- To discuss future directions for novel PET tracer development.
- To highlight the need for tracers targeting specific protein aggregates like Lewy bodies.
Main Methods:
- Review of existing literature on PET tracer development for neurodegenerative diseases.
- Analysis of challenges and successes in amyloid and tau PET tracer development.
- Discussion of potential strategies for developing new tracers.
Main Results:
- Amyloid and tau PET tracers are clinically available and widely used.
- Off-target binding and neuroinflammation can affect tau PET tracer accuracy.
- There is a lack of established PET tracers for imaging Lewy bodies.
Conclusions:
- PET imaging has revolutionized the study of proteinopathies.
- Further development is needed to overcome limitations in current tracers, particularly for Lewy body diseases.
- Future PET tracer development should focus on specificity and addressing confounding factors like neuroinflammation.
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