Unraveling protein dynamics to understand the brain - the next molecular frontier

Kyle D Brewer; Sophia M Shi; Tony Wyss-Coray

doi:10.1186/s13024-022-00546-8

Unraveling protein dynamics to understand the brain - the next molecular frontier

Mol Neurodegener. 2022 Jun 18;17(1):45. doi: 10.1186/s13024-022-00546-8.

Authors

Kyle D Brewer^#^{1

2

3}, Sophia M Shi^#^{1

2

3

4}, Tony Wyss-Coray^{5

6

7

8}

Affiliations

¹ ChEM-H, Stanford University, Stanford, CA, USA.
² Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA.
³ Wu Tsai Neurosciences Institute, Stanford University, Stanford, CA, USA.
⁴ Department of Chemistry, Stanford University, Stanford, CA, USA.
⁵ ChEM-H, Stanford University, Stanford, CA, USA. twc@stanford.edu.
⁶ Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA. twc@stanford.edu.
⁷ Wu Tsai Neurosciences Institute, Stanford University, Stanford, CA, USA. twc@stanford.edu.
⁸ Phil and Penny Knight Initiative for Brain Resilience, Stanford University, Stanford, CA, USA. twc@stanford.edu.

^# Contributed equally.

Abstract

The technological revolution to measure global gene expression at the single-cell level is currently transforming our knowledge of the brain and neurological diseases, leading from a basic understanding of genetic regulators and risk factors to one of more complex gene interactions and biological pathways. Looking ahead, our next challenge will be the reliable measurement and understanding of proteins. We describe in this review how to apply new, powerful methods of protein labeling, tracking, and detection. Recent developments of these methods now enable researchers to uncover protein mechanisms in vivo that may previously have only been hypothesized. These methods are also useful for discovering new biology because how proteins regulate systemic interactions is not well understood in most cases, such as how they travel through the bloodstream to distal targets or cross the blood-brain barrier. Genetic sequencing of DNA and RNA have enabled many great discoveries in the past 20 years, and now, the protein methods described here are creating a more complete picture of how cells to whole organisms function. It is likely that these developments will generate another transformation in biomedical research and our understanding of the brain and will ultimately allow for patient-specific medicine on a protein level.

Keywords: Bioorthogonal labeling; Blood–brain barrier; Mass spectrometry; Plasma; Protein labeling; Protein tracking; Proteomics.

Publication types

Review
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Brain*
Humans
Proteins*

Substances

Proteins

Grants and funding

R01 AG072255/AG/NIA NIH HHS/United States