Figure 6. Proposed scenario for the fate of transgenically expressed TTR in the fly.

Soluble TTR is expressed in the retina and secreted to the hemolymph where it undergoes misfolding and initial aggregation/oligomerization. Fat body cells take up TTR conformers from the circulation and pack them tightly into aggregates of a few microns size consisting of nanospherules and nanofilaments. This leads to cell death of fat body cells and hypotrophy of the tissue, releasing TTR aggregates and filaments back to the hemolymph. Aggregates formed in the hemolymph at early stages represent the neurotoxic fraction of TTR, whereas aggregates and filaments present in hemolymph at late stages do not exhibit cell toxicity. Thus, the fat body neutralizes toxicity of TTR conformers by uptake from hemolymph and assists their maturation to the detriment of its integrity.