Mapping the human brain proteome: opportunities, challenges, and clinical potential

Area of Science:

• Neuroscience
• Biochemistry
• Molecular Biology

Background:

• The human brain's complexity necessitates understanding molecular profiles in specific regions and biofluids.
• Neurodegenerative and psychiatric diseases are linked to molecular imbalances within the brain.
• Current knowledge relies on neurophysiology, anatomy, and transcriptomics.

Purpose of the Study:

• To highlight the essential role of molecular profiling in understanding brain structure specialization.
• To investigate the molecular basis of imbalances in neurodegenerative and psychiatric diseases.
• To explore the potential of proteomics in identifying biomarkers and therapeutic targets.

Main Methods:

• Advanced proteomics techniques, including laser capture and imaging proteomics.
• Liquid chromatography-tandem mass spectrometry (LC-MS/MS) developments.
• Antibody/aptamer-based platforms for novel dimension generation.

Main Results:

• Proteomics enables functional characterization, quantification, and localization of brain proteins.
• New dimensions in cellular, spatial, and posttranslational analysis are now possible.
• Biomarker validation and druggable target identification are enhanced.

Conclusions:

• Elucidating multi-dimensional protein homeostasis is crucial for maintaining cognitive functions.
• Comprehensive pathological proteomes can inform drug-repositioning strategies.
• Proteomics provides innovative avenues for neurodegenerative and psychiatric disorder therapies.