Hormesis, Cell Death, and Regenerative Medicine for Neurodegenerative Diseases

Abstract

ᮀ Although the adult human brain has a small number of neural stem cells, they are insufficient to repair the damaged brain to achieve significant functional recovery for neurodegenerative diseases and stroke. Stem cell therapy, by either enhancing endogenous neurogenesis, or transplanting stem cells, has been regarded as a promising solution. However, the harsh environment of the diseased brain posts a severe threat to the survival and correct differentiation of those new stem cells. Hormesis (or preconditioning, stress adaptation) is an adaptation mechanism by which cells or organisms are potentiated to survive an otherwise lethal condition, such as the harsh oxidative stress in the stroke brain. Stem cells treated by low levels of chemical, physical, or pharmacological stimuli have been shown to survive better in the neurodegenerative brain. Thus combining hormesis and stem cell therapy might improve the outcome for treatment of these diseases. In addition, since the cell death patterns and their underlying molecular mechanism may vary in different neurodegenerative diseases, even in different progression stages of the same disease, it is essential to design a suitable and optimum hormetic strategy that is tailored to the individual patient.

Berberine protects against 6-OHDA-induced neurotoxicity in PC12 cells and zebrafish through hormetic mechanisms involving PI3K/AKT/Bcl-2 and Nrf2/HO-1 pathways

“…Hormesis is defined as a biphasic dose-response phenomenon that is characterized by a low-dose beneficial or stimulatory response and a high-dose toxic or inhibitory response, which has been observed in a broad range of biological and physiological systems [1], [2], [3]. According to the principles of hormesis, exposure to low concentrations of drugs, toxins or natural substances may protect against damage from a subsequent stressor, while at higher dose the toxic effect prevails [1], [4].…”

“…Hormesis has the potential to improve the quality of life during the normal lifespan, such as memory enhancement, bone strengthening, anxiety reduction, and protection against agonists inducing neuronal diseases [4], [6]. Recently, the hormesis concept has been receiving increasing attention in the field of neuroscience, including the areas of neuroprotection, and drugs for Parkinson's disease (PD), Alzheimer's disease (AD), Huntington's disease (HD), as well as in the areas of behavioral pharmacology [1], [3], [4].…”

Tryptophan and Cell Death

“…Cell death patterns and their underlying molecular mechanisms may be different in various diseases and even in different progression stages of the same disease (Wang 2012 ). Death-associated protein kinases (DAPKs) regulate many signaling events of the cell death pathways, including apoptosis, autophagy, and membrane blebbing (Bovellan et al 2010 ).…”

Oleanolic Acid Enhances the Beneficial Effects of Preconditioning on PC12 Cells

“…During preconditioning bioprotective mechanisms that include induction of cytoprotective pathways (molecular chaperones), antioxidative systems, DNA repair systems, and immune system are stimulated. These molecular mechanisms have been shown to protect cells from various forms of cell death [ 4 , 5 ].…”

“…Despite numerous studies its management remains unsatisfactory. Cell based therapy is one of the emerging treatments of Parkinson's disease and its use has grown in promise since certain stem cells have also been shown to have the ability to enhance endogenous neurogenesis [ 5 ]. However, the harsh environment of the diseased brain is a severe threat to the survival and/or correct differentiation of these implanted cells [ 5 ].…”