How Do Subcellular Organelles Participate in Preconditioning-Conferred Neuroprotection?
Preconditioning or tolerance is a natural phenomenon of endogenous adaptation, whereby subtoxic stress protects against subsequent higher dose stress. Although preconditioning is likely to be a ubiquitous stress response relevant to many disease conditions, it has been most successfully employed in ischemia research. Enormous efforts have focused on identifying the intrinsic mechanisms so that they can be translated into pharmacological interventions aimed at counteracting neurodegeneration following stroke. A firm grasp of the molecular events at the level of each subcellular organelle will aid researchers to move closer towards this elusive clinical goal. Fortunately, technological innovations such as the confocal and transmission electron microscopes have transported preconditioning research into the subcellular organelle level. This has deepened our knowledge of how preconditioning affects these organelles and triggers subcellular signaling pathways that eventually lead to neuroprotective processes and cellular survival. In this chapter, the participation of mitochondria, the endoplasmic reticulum, proteasomes, lysosomes, the Golgi apparatus, the peroxisome proliferator-activated receptors on the nuclear membrane, and gene expression regulating factors in the nucleus will thus be considered.
KeywordsEndoplasmic Reticulum Stress Reactive Oxygen Species Generation Unfold Protein Response Ischemic Precondition Mitochondrial Biogenesis
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