USE OF CALCILYTIC DRUGS AS A PHARMACOLOGICAL APPROACH TO THE TREATMENT AND PREVENTION OF ALZHEIMERS DISEASE, ALZHEIMERS DISEASE-RELATED DISORDERS, AND DOWNS SYNDROME NEUROPATHIES
A pharmacological treatment of both familial early onset and sporadic late onset Alzheimers disease (AD), AD-related disorders and Downs syndrome-coupled neuropathies involves the use of a class of drugs, the calcilytics, which by inhibiting the calcium-sensing receptor (CaSR)signaling in all types of brain cells prevent: (i) the overproduction of cell-harming nitric oxide (NO) and peroxynitrite (ONOO-), and most importantly (ii) the intracellular overproduction, accumulation, and secretion of Amyloid beta (Abeta) peptides in response to the extracellular presence of exogenous Abetapeptides and/or proinflammatory cytokines, and (iii) the Abeta peptide-related hyperphosphorylation of the Tau (tau) protein on the part of an Abeta/Ca SR-signaling activated glycogen synthase kinase-(GSK)-3beta w i t h the resulting formation of neurofibrillary tangles (NTFs), the latter known to cause such severe dysfunctioning of the microtubular cytoskeleton as to eventually favor (iv) the death of human cerebral cortex neurons.
