Proximity labeling in neuroscience: decoding molecular landscapes for precision neurology

Area of Science:

• Neuroscience
• Molecular Biology
• Biochemistry

Background:

• Neurological disease research is hindered by complex cellular interactions.
• Conventional methods fail to detect transient, low-affinity, or localized molecular events.
• Proximity labeling (PL) offers a solution for in situ molecular event capture.

Purpose of the Study:

• To review proximity labeling principles and applications in neuroscience.
• To highlight PL's role in understanding brain function and disease.
• To discuss PL's potential in advancing precision neurology and therapeutics.

Main Methods:

• Spatially restricted biotinylation using engineered biotin ligases (e.g., TurboID) and peroxidases (e.g., APEX2).
• Emerging photocatalytic platforms for proximity labeling.
• High-resolution mapping of proteomes and interactomes within specific cellular contexts.

Main Results:

• PL enables detailed mapping of proteomes and interactomes in defined subcellular compartments, cell types, and interfaces.
• PL elucidates pathophysiological mechanisms in Alzheimer's disease, Parkinson's disease, and other neurological disorders.
• PL facilitates discovery of mechanistic biomarkers and druggable targets for clinical translation.

Conclusions:

• Proximity labeling revolutionizes molecular atlasing of the nervous system.
• PL accelerates understanding of brain function and neurological disease pathogenesis.
• PL advances precision neurology by integrating molecular insights with therapeutic innovation.