Ironjustic
Mon, Nov-20-06, 06:15
Curr Pharm Des. 2006;12(27):3521-33. Links Dual effects of
antioxidants in neurodegeneration: direct neuroprotection
against oxidative stress and indirect protection via
suppression of glia-mediated inflammation.Wang JY, Wen LL,
Huang YN, Chen YT, Ku MC. Department of Physiology, National
Defense Medical Center, 161, Sec.6, Ming-Chuan E. Rd. Taipei,
Taiwan, R.O.C. jywang@ndmctsgh.edu.tw
Oxidative stress, in which production of highly reactive
oxygen species (ROS) and reactive nitrogen species (RNS)
overwhelms antioxidant defenses, is a feature of many
neurological diseases and neurodegeneration. ROS and RNS
generated extracellularly and intracellularly by various
processes initiate and promote neurodegeneration in CNS. ROS
and RNS can directly oxidize and damage macromolecules such as
DNA, proteins, and lipids, culminating in neurodegeneration in
the CNS. Neurons are most susceptible to direct oxidative
injury by ROS and RNS. ROS and RNS can also indirectly
contribute to tissue damage by activating a number of cellular
pathways resulting in the expression of stress-sensitive genes
and proteins to cause oxidative injury. Moreover, oxidative
stress also activates mechanisms that result in a
glia-mediated inflammation that also causes secondary neuronal
damage. Associated with neuronal injuries caused by many CNS
insults is an activation of glial cells (particularly
astrocytes and microglia) at the sites of injury. Activated
glial cells are thus histopathological hallmarks of
neurodegenerative diseases. Even though direct contact of
activated glia with neurons per se may not necessarily be
toxic, the immune mediators (e.g. nitric oxide and reactive
oxygen species, pro-inflammatory cytokines and chemokines)
released by activated glial cells are currently considered to
be candidate neurotoxins. Therefore, study of the protective
role of antioxidant compounds on inhibition of the
inflammatory response and correcting the fundamental
oxidant/antioxidant imbalance in patients suffering from
neurodegenerative diseases are important vistas for further
research. The purpose of this review is to summarize the
current evidence in support of this critical role played by
oxidative stress of neuronal and glial origin in
neurodegenerative diseases. The mechanistic basis of the
neuroprotective activity of antioxidants does not only rely on
the general free radical trapping or antioxidant activity per
se in neurons, but also the suppression of genes induced by
pro-inflammatory cytokines and other mediators released by
glial cells. We propose that combinations of agents which act
at sequential steps in the neurodegenerative process can
produce additive neuroprotective effects. A cocktail of
multiple antioxidants with anti-inflammatory agents may be
more beneficial in the prevention of neurodegenerative
disease. A clearer appreciation of the potential therapeutic
utility of antioxidants would emerge only when the complexity
of their effects on mechanisms that interact to determine the
extent of oxidative damage in vivo are more fully defined and
understood.
PMID: 17017945 [PubMed - in process]
Who loves ya. Tom
Jesus Was A Vegetarian! http://jesuswasavegetarian.7h.com
Man Is A Herbivore! http://tinyurl.com/a3cc3
DEAD PEOPLE WALKING http://tinyurl.com/zk9fk
antioxidants in neurodegeneration: direct neuroprotection
against oxidative stress and indirect protection via
suppression of glia-mediated inflammation.Wang JY, Wen LL,
Huang YN, Chen YT, Ku MC. Department of Physiology, National
Defense Medical Center, 161, Sec.6, Ming-Chuan E. Rd. Taipei,
Taiwan, R.O.C. jywang@ndmctsgh.edu.tw
Oxidative stress, in which production of highly reactive
oxygen species (ROS) and reactive nitrogen species (RNS)
overwhelms antioxidant defenses, is a feature of many
neurological diseases and neurodegeneration. ROS and RNS
generated extracellularly and intracellularly by various
processes initiate and promote neurodegeneration in CNS. ROS
and RNS can directly oxidize and damage macromolecules such as
DNA, proteins, and lipids, culminating in neurodegeneration in
the CNS. Neurons are most susceptible to direct oxidative
injury by ROS and RNS. ROS and RNS can also indirectly
contribute to tissue damage by activating a number of cellular
pathways resulting in the expression of stress-sensitive genes
and proteins to cause oxidative injury. Moreover, oxidative
stress also activates mechanisms that result in a
glia-mediated inflammation that also causes secondary neuronal
damage. Associated with neuronal injuries caused by many CNS
insults is an activation of glial cells (particularly
astrocytes and microglia) at the sites of injury. Activated
glial cells are thus histopathological hallmarks of
neurodegenerative diseases. Even though direct contact of
activated glia with neurons per se may not necessarily be
toxic, the immune mediators (e.g. nitric oxide and reactive
oxygen species, pro-inflammatory cytokines and chemokines)
released by activated glial cells are currently considered to
be candidate neurotoxins. Therefore, study of the protective
role of antioxidant compounds on inhibition of the
inflammatory response and correcting the fundamental
oxidant/antioxidant imbalance in patients suffering from
neurodegenerative diseases are important vistas for further
research. The purpose of this review is to summarize the
current evidence in support of this critical role played by
oxidative stress of neuronal and glial origin in
neurodegenerative diseases. The mechanistic basis of the
neuroprotective activity of antioxidants does not only rely on
the general free radical trapping or antioxidant activity per
se in neurons, but also the suppression of genes induced by
pro-inflammatory cytokines and other mediators released by
glial cells. We propose that combinations of agents which act
at sequential steps in the neurodegenerative process can
produce additive neuroprotective effects. A cocktail of
multiple antioxidants with anti-inflammatory agents may be
more beneficial in the prevention of neurodegenerative
disease. A clearer appreciation of the potential therapeutic
utility of antioxidants would emerge only when the complexity
of their effects on mechanisms that interact to determine the
extent of oxidative damage in vivo are more fully defined and
understood.
PMID: 17017945 [PubMed - in process]
Who loves ya. Tom
Jesus Was A Vegetarian! http://jesuswasavegetarian.7h.com
Man Is A Herbivore! http://tinyurl.com/a3cc3
DEAD PEOPLE WALKING http://tinyurl.com/zk9fk