Pathological Brain Iron

[ironjustice]

Suppression of glial HO-1 activity as a potential
neurotherapeutic intervention in AD.
Schipper HM, Gupta A, Szarek WA.
Centre for Neurotranslational Research and Bloomfield
Centre for Research in Aging,
The Lady Davis Institute for Medical Research,
Sir Mortimer B. Davis Jewish General Hospital,
McGill University, Montreal, Quebec, Canada.
hyman.s...@mcgill.ca

The mechanisms responsible for oxidative damage,
pathological brain iron deposition and mitochondrial
insufficiency in Alzheimer disease (AD) remain enigmatic.
Heme oxygenase-1 (HO-1) is a 32 kDa stress protein that
catabolizes heme to biliverdin, free iron and carbon
monoxide.
The HO-1 gene is exquisitely sensitive to oxidative
stress and is induced in brain and other tissues in
various models of disease and trauma.
Our laboratory demonstrated that
1) HO-1 protein is significantly over-expressed in
AD-affected temporal cortex and hippocampus relative
to neurohistologically-normal control preparations,
2) in cultured astrocytes, HO-1 up-regulation by
transient transfection of the human ho-1 gene, or
stimulation of endogenous HO-1 expression by exposure
to beta-amyloid, TNFalpha or IL-1beta, promotes
intracellular oxidative stress, opening of the
mitochondrial permeability transition pore and
accumulation of non-transferrin iron in the
mitochondrial compartment, and
3) the glial iron sequestration renders co-cultured
neuron-like PC12 cells prone to oxidative injury.
Induction of the astroglial ho-1 gene may constitute
a 'common pathway' leading to pathological brain iron
deposition, intracellular oxidative damage and
bioenergetic failure in AD and other human CNS
disorders.
HYPOTHESIS:
Targeted suppression of glial HO-1 hyperactivity
may prove to be a rational and effective
neurotherapeutic intervention in AD and related
neurodegenerative disorders.
To begin testing this hypothesis, studies have been
initiated to determine whether systemic administration
of a novel, selective and brain-permeable inhibitor
of HO-1 activity ameliorates cognitive dysfunction
and neuropathology in a transgenic mouse model of AD.

PMID: 19874266

Who loves ya.
Tom

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[fer...@paris.com]

Ho hum, another iron follows the disorder tale. This makes it a
refutation of the iron idea just as the many previous posts were the
case.. The many confusions of the dog and the tail. That was a pun
son,
a pun.