engleski

Aggregation of TRIOBP-1 and schizophrenia: Identification of a distinct aggregation domain

Aims: Many neurodegenerative conditions are characterised by the accumulation of insoluble aggregates of specific proteins in the brain, and we hypothesised that such proteins may also exist in chronic mental illness. Our aim was to identify and characterise such a protein. Methods: The total insoluble protein fraction (“aggregome”) was purified from brain samples from patients with schizophrenia and used to immunise a mouse. Monoclonal antibodies were raised from this animal and tested for those that recognised the original schizophrenia brain aggregome over an equivalent preparation from control individuals. The antigen for this antibody was identified through proteomics, and its propensity to aggregate investigated in cell culture assays. Results: An antibody specific for aggregated protein in the schizophrenia brain sample was identified, with the protein TRIOBP-1 as its primary antigen. TRIOBP-1 was confirmed to have a natural tendency to aggregate in cell lines and primary neurons. Expression of fragments of the protein in isolation further demonstrated this aggregation propensity to be dependent on a stretch of 25 amino acids near to the centre of the protein. Conclusions: We propose that TRIOBP-1 is a protein which can form insoluble protein aggregates in the brains of at least a subset of patients with major mental illness, and that its aggregation appears to occur via a specific cellular mechanism, associated with a 25 amino acid stretch within the protein TRIOBP-1. Replication assays to confirm the presence of TRIOBP-1 aggregates in brain samples from other patients with major mental illness are currently underway.

TRIOBP ; Tara ; Aggregation ; Mental illness ; Schizophrenia

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