Transition from physiological to pathophysiological indices as exemplified by amyloidosis in periodic disease, non-insulin-dependent diabetes mellitus, and Alzheimer’s disease

Theoretical studies on amyloidosis have been performed. The results promote understanding of primary causes and molecular mechanisms of the formation of pathological protein and permits tracing the transitions from physiological indices to pathological ones in periodic disease (PD), non-insulin-dependent diabetes mellitus (NIDDM), and Alzheimer’s disease (AD). Blockage of the biochemical target by a biologically active substance (drug) at the initial stage of disease makes it possible to avoid formation of pathology. The concept of a “situational physiological skip” is introduced. A new class of drugs (situational controllers of metabolism) that affect transitions from the normal state to pathology in initial periods of disease can be developed. The rational way of finding the prototype of a new drug with a new mechanism of action is computer-aided the developmenrt of a drug on the basis of the spatial structure the target protein. The development of inner structure of proteins related to pathology should be based on distinct grouping of patients according to their genotypes and phenotypes.