FIGURE 2.

The polygon of self-destructive forces. Every angle of this octagon represents a pathophysiological process closely related to almost all of the others, and each pathological process is known to be involved in several illnesses of civilization (see Table 1) with extensive overlap (e.g., Alzheimer’s disease has chronic low grade inflammation, increased nitric oxide signaling, calcium dyshomeostasis, apoptosis, mitochondrial dysfunction, oxidative, and endoplasmic reticulum stress in its etiopathology). The central position of the Sig-1R illustrates its significant influence in mitigating these pathological processes. The number of angles is rather arbitrary: one may add others like insulin resistance, glutamate release, plasma membrane deficiency, etc.