Neuroprotective Role of Mitochondrial Uncoupling Protein 2 in Cerebral Stroke

Abstract

The uncoupling proteins (UCPs) are mitochondrial transporter proteins involved in proton conductance across inner mitochondrial membrane (IMM). UCP2, which is one of the members of this class of proteins, has a wide but restricted tissue distribution including brain. Its physiologic role according to emerging evidences, although still not clear, indicate that distribution of UCP2 may be related to regulation of mitochondria membrane potential (DWm), production of reactive oxygen species (ROS), preservation of calcium homeostasis, modulation of neuronal activity, and eventually inhibition of cellular damage. These factors are very important in determining the fate of neurons and damage progression in the brain during various neurodegenerative diseases including cerebral stroke. Recent evidence indicates that an increased expression and activity of UCP2 are well correlated with neuronal survival after stroke and trauma. This review briefly covers the present understanding of UCP2, which eventually may be beneficial to understand the precise role of UCP2 to develop strategy to identify its potential therapeutic application.

Expression of Mitochondrial Uncoupling Protein UCP2 in the Brain of Rats after Hippocampal Injury Inflicted by Kainic Acid

“…As was noted above, the physiological role of UCP2 remains not quite clear, but experimental fi ndings indicate its involvement in the regulation of the mitochondrial membrane potential, production of active oxygen species, stabilization of calcium homeostasis, modulation of neuronal activity, and eventually reduction of cell injury [9]. It was found, for example, that higher expression of UCP2 correlated with neuronal survival after stroke and injury [10,11]. Increase of UCP2 expression in the brain under the effect of KA was observed by other authors [5].…”

Amitriptyline Improves Motor Function via Enhanced Neurotrophin Signaling and Mitochondrial Functions in the Murine N171-82Q Huntington Disease Model

“…Both VDAC and complex IV are regarded as classic mitochondrial markers, suggesting that AMI treatment has provided considerable mitochondrial support in these mice. PGC-1␣ plays a critical role in regulating mitochondrial biogenesis and functionality (74), whereas UCP2 is known for its role in maintaining the mitochondrial membrane potential and preventing insults from free radicals (75). Further evidence has shown that UCP2 is capable of eliciting neuroprotective effects in neurodegenerative diseases (76) and traumatic central nervous system events such as stroke (77).…”

Alterations in anxiety-like behavior following knockout of the uncoupling protein 2 (ucp2) gene in mice

“…UCP2 is expressed in a wide variety of tissues, including the brain (Richard et al, 1998;Richard et al, 2001). Here, UCP2 prevents neuronal death and diminishes brain dysfunction after stroke and brain trauma (Mattiasson et al, 2003;Mehta and Li, 2009). The ucp2 gene has been identified as a susceptibility gene in multiple sclerosis (MS) (Vogler et al, 2005).…”