**Conflict of interest**

The author declares no conflict of interest.

*Pathophysiology of Amyloid Fibril Formation DOI: http://dx.doi.org/10.5772/intechopen.81965*

*Amyloid Diseases*

and related conditions.

the problem(s) and the options.

**Acknowledgements**

**Conflict of interest**

**7. Conclusions**

For TTR-related disorders several approaches are recognized. First, because the liver is the main site for the synthesis of TTR, liver transplantation can eliminate production of the mutant TTR protein. Although this has been used successfully, it is a complex process with its own intrinsic short- and long-term complications [24]. Second, synthesis of the responsible mutant protein can be suppressed. Several approaches based on specifically interrupting stability of TTR messenger RNA through RNAi have been developed. (Carriers of TTR mutations are usually heterozygotes, so these approaches generally reduce levels of both mutant and normal TTR—apparently, a reduced concentration of TTR is well-tolerated.) Third, the circulating tetramer can be stabilized by exogenous agents (e.g., Tafamidis™) to shift the equilibrium away from dissociation (and, hence, minimize oligomer

For neurologic disorders where the underlying problem is likely intracellular (e.g., α-synuclein and β-protein), the above approaches have not been feasible. It is more likely that clarification of complex intracellular pathways will be required in order to develop approaches to prevent and/or interrupt fibril accumulation in these

Amyloid formation and related disorders present examples of situations where there is fundamental dependence on protein structure, its variation(s), abundance, and the consequences of alternative conformation(s). Because the molecules involved are quite different for each type of amyloid disease, different organs may be involved, and stabilizing or eliminating the precursors likely will vary. Successful therapeutic intervention will likely be unique to each type of amyloidosis. The basic concerns are similar, however, and considerable progress has already clarified both

Support for these studies was provided by generous gifts to the author from Stuart

Bainum, Mary Nell and George A. Berry, Ethelbert Cooper, Gloria and Edward Felsenthal, Ruth Frey, Shirley Griffin, Ruth and George Harms, Yancey and David Hillegas, Diantha Johnson, Bassem Kudsi, Steven Lazinsky, Judy Lewent and Mark Shapiro, Terrence O'Donnell, Jay Ripley, Israel Vainboim, the Foundation for Greater

Good, the Health Network Foundation, and the MetLife Foundation.

The author declares no conflict of interest.

formation). These approaches show promise [25, 26].

**184**
