Hormesis-induced neuroplasticity: Targeting neuroinflammation signaling cascades for therapeutic insights in aging and neurodegenerative diseases.

The signaling pathways associated with α-Klotho, glutamate, mediators of the inflammatory response in the central nervous system (CNS) and that related to different isoforms of the Na, K-ATPase (NKA) protein as a pump and receptor for endogenous steroids (ouabain-like hormones) are associated with neuroplasticity and neuroprotection. This neuroadaptive response induced by pharmacologic (Cardiotonic Steroids, Klotho, Resveratrol, Curcumin, and other Phytochemicals), and non-pharmacologic strategies (intermittent fasting and physical exercise) involves glial and neuronal cell crosstalk through activation of different intracellular pathways involving mediators, such as glutamate, cytokines, transcription factors, and gene expression which will exert a marked influence on the adaptive processes (neuroplasticity) that prevent premature aging, in addition to playing an essential role in cognition and neurodegenerative processes. The present text addresses the effect of these agents on the Central Nervous System (CNS), exploring neuroplasticity changes associated with the neuroinflammation induced by these mediators in the presence of a modified expression or signaling of the α-Klotho and the different α-isoforms of NKA. The studies involve in vitro approaches using models of neuronal and glial cells and in vivo studies with a behavioral and biochemical approach. Studies were also done in the presence (or absence) of changes in the expression of these proteins (by using vectors, interference RNA, and transgenic animals with specific protein-modified expression, such as TNF-α and Klotho). It has been also several human studies evaluating these hermetic strategies associated with physical exercise and intermittent diet. The present chapter discusses the benefit of these strategies in the induction of neuroadaptive response.