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Co-Aggregation and Parallel Aggregation of Specific Proteins in Major Mental Illness
Bobana Samardžija1, Maja Juković1, Beti Zaharija1
1Department of Biotechnology, University of Rijeka, 51000 Rijeka, Croatia.
Cells
|July 29, 2023
Summary
Protein aggregation in major depressive disorder brains is common, but proteins like DISC1, CRMP1, and TRIOBP-1 usually aggregate independently rather than co-aggregating. This finding is crucial for understanding mental illness pathology and developing future treatments.
Area of Science:
- Neuroscience
- Molecular Biology
- Psychiatry
Background:
- Disrupted proteostasis is linked to major depressive disorder (MDD).
- Proteins like CRMP1, DISC1, NPAS3, and TRIOBP-1 are implicated in psychiatric illness-related brain aggregates.
- The aggregation patterns (parallel vs. co-aggregation) of these proteins in MDD are not well understood.
Purpose of the Study:
- To investigate whether specific proteins aggregate together in the brains of MDD patients.
- To determine if these proteins co-aggregate (physically interact) or aggregate independently (parallel aggregation).
Main Methods:
- Post-mortem insular cortex samples from MDD patients, Alzheimer's disease patients, suicide victims, and controls were analyzed.
- Western blotting identified insoluble protein fractions.
- Pairwise protein expression in SH-SY5Y neuroblastoma cells and immunofluorescent microscopy assessed co-aggregation.
Main Results:
- Multiple insoluble proteins were found in many individuals, but not enough to confirm interaction.
- Cell culture showed DISC1 co-aggregates with CRMP1 and TRIOBP-1.
- DISC1 induced aggregation of full-length TRIOBP-1, but not its individual domains.
Conclusions:
- While some protein co-aggregation occurs (e.g., DISC1 with CRMP1/TRIOBP-1), parallel aggregation is more common in mental illness.
- Understanding these aggregation mechanisms is vital for developing diagnostics and therapeutics for mental illnesses.
