title: Osteoporosis and alzheimer pathology: Role of cellular stress response and hormetic redox signaling in aging and bone remodeling.
abstract: Alzheimer's disease (AD) and osteoporosis are multifactorial progressive degenerative disorders. Increasing evidence shows that osteoporosis and hip fracture are common complication observed in AD patients, although the mechanisms underlying this association remain poorly understood. Reactive oxygen species (ROS) are emerging as intracellular redox signaling molecules involved in the regulation of bone metabolism, including receptor activator of nuclear factor-κB ligand-dependent osteoclast differentiation, but they also have cytotoxic effects that include lipoperoxidation and oxidative damage to proteins and DNA. ROS generation, which is implicated in the regulation of cellular stress response mechanisms, is an integrated, highly regulated, process under control of redox sensitive genes coding for redox proteins called vitagenes. Vitagenes, encoding for proteins such as heat shock proteins (Hsps) Hsp32, Hsp70, the thioredoxin, and the sirtuin protein, represent a systems controlling a complex network of intracellular signaling pathways relevant to life span and involved in the preservation of cellular homeostasis under stress conditions. Consistently, nutritional anti-oxidants have demonstrated their neuroprotective potential through a hormetic-dependent activation of vitagenes. The biological relevance of dose-response affects those strategies pointing to the optimal dosing to patients in the treatment of numerous diseases. Thus, the heat shock response has become an important hormetic target for novel cytoprotective strategies focusing on the pharmacological development of compounds capable of modulating stress response mechanisms. Here we discuss possible signaling mechanisms involved in the activation of vitagenes which, relevant to bone remodeling and through enhancement of cellular stress resistance provide a rationale to limit the deleterious consequences associated to homeostasis disruption with consequent impact on the aging process.
authors: Department of Chemistry, University of Catania Catania, Italy ; Department of Clinical and Experimental Medicine and Pharmacology, School of Medicine Messina, Italy.
authors: Carolin
authors: C
authors: Cornelius
authors: Department of Biomedical Sciences, University of Catania Catania, Italy.
authors: Guido
authors: G
authors: Koverech
authors: Department of Clinical and Experimental Medicine and Pharmacology, School of Medicine Messina, Italy.
authors: Rosalia
authors: R
authors: Crupi
authors: Department of Clinical and Experimental Medicine and Pharmacology, School of Medicine Messina, Italy.
authors: Rosanna
authors: R
authors: Di Paola
authors: Department of Biomedical Sciences, University of Catania Catania, Italy.
authors: Angela
authors: A
authors: Koverech
authors: Department of Biomedical Sciences, University of Catania Catania, Italy.
authors: Francesca
authors: F
authors: Lodato
authors: Department of Biomedical Sciences, University of Catania Catania, Italy.
authors: Maria
authors: M
authors: Scuto
authors: Department of Biomedical Sciences, University of Catania Catania, Italy.
authors: Angela T
authors: AT
authors: Salinaro
authors: Department of Clinical and Experimental Medicine and Pharmacology, School of Medicine Messina, Italy ; University of Manchester Manchester, UK.
authors: Salvatore
authors: S
authors: Cuzzocrea
authors: Environmental Health Sciences Division, School of Public Health, University of Massachusetts Amherst, MA, USA.
authors: Edward J
authors: EJ
authors: Calabrese
authors: Department of Biomedical Sciences, University of Catania Catania, Italy.
authors: Vittorio
authors: V
authors: Calabrese
keywords: Alzheimer’s disease; cellular stress response; hormesis; oxidative stress; redox status; vitagenes