Nrf2 as a Therapeutic Target for Stroke and Neurodegeneration

Stroke is a leading cause of death and disability in
North America.
One major cause of nerve tissue damage during stroke
is the
accumulation of reactive oxygen species- molecules
that steal
electrons from healthy cells in a process known as
oxidation. This
thesis describes a novel approach to increase
antioxidant levels in
order to maintain oxidative balance and prevent
cellular damage
during stroke. The stress-responsive transcription
factor, Nrf2, is
able to launch the endogenous mechanisms of cellular
defense and
repair. Nrf2 represents a master switch that
coordinates tens to
hundreds of antioxidant and detoxification genes
working in
synergy. In rodent models of stroke and
neurodegeneration,
increased Nrf2 activity was found to promote neuronal
survival and
improve recovery of limb function weeks to months
following injury.
Interestingly, a number of molecules that activate
Nrf2 are found in
cruciferous vegetables, such as broccoli sprouts,
suggesting the
possibility of practical diet-based therapies.

Autorentext

Andy received his Ph.D. in Neuroscience at the University ofBritish Columbia with Dr. Tim Murphy. He is currently working as a post-doctoral fellowwith Dr. David Kleinfeld at the University of California, San Diego. His presentresearch uses novel imaging techniques to study reactivity of arterioles in therodent brain.

Klappentext

Stroke is a leading cause of death and disability inNorth America. One major cause of nerve tissue damage during strokeis the accumulation of reactive oxygen species- moleculesthat steal electrons from healthy cells in a process known asoxidation. This thesis describes a novel approach to increaseantioxidant levels in order to maintain oxidative balance and preventcellular damage during stroke. The stress-responsive transcriptionfactor, Nrf2, is able to launch the endogenous mechanisms of cellulardefense and repair. Nrf2 represents a master switch thatcoordinates tens to hundreds of antioxidant and detoxification genesworking in synergy. In rodent models of stroke andneurodegeneration, increased Nrf2 activity was found to promote neuronalsurvival and improve recovery of limb function weeks to monthsfollowing injury. Interestingly, a number of molecules that activateNrf2 are found in cruciferous vegetables, such as broccoli sprouts,suggesting the possibility of practical diet-based therapies.