On Mar 6, 7:32 am, "ironjust...@aol.com" <ironjust...@aol.com> wrote:
iron-loaded human
transferrin <<

One could assume then .. non-iron-loaded transferrin .. doesn't ..
"aggregate into long wormlike
fibrils" .."in a similar fashion in the brain."

Transferrin has been shown to not .. 'leak' WHEN it is 25% full .. but
it seems above that .. point .. it just may ..
"no longer properly enclosed;" .. and .. "instead,
they aggregate into periodically arranged nanocrystals whose
structure
seems to be very similar to the iron oxide mineral lepidocrocite".

----------------------------------------------

Nature Reviews Drug Discovery 2, 338 (2003); doi:10.1038/nrd1102

[557K]

NEURODEGENERATIVE DISEASES
Ferritin out iron's role

Adam Smith

The amount of iron in the brain increases with normal ageing, but
elevated
iron levels are also associated with several neurodegenerative
diseases,
including Parkinson's disease. Reactive ferrous iron (Fe2+) can
participate in
the
generation of cell-damaging free radicals, so it has been hypothesized
that
higher iron concentrations could play a part in the neuronal loss
observed
both in
old age and, more drastically, in many diseases. However, as with many
of the
other observed biochemical and pathological changes that accompany
neurodegenerative diseases, there is debate as to whether increasing
iron
levels
themselves cause cellular damage, or are simply a consequence of
damage caused
by
other factors. Convincing evidence for the detrimental effects of
elevated
iron
in an acute animal model of Parkinson's disease is now presented in a
study
published in the March 27th issue of Neuron, in which Kaur et al. show
that
brain
damage is diminished by reducing iron levels.

The authors used both transgenic and pharmacological methods to
sequester
iron in mice that were exposed to one or more doses of the neurotoxin
MPTP,
the
standard method for producing animal models that mimic many of the
signs of
Parkinson's disease. In the transgenic approach, the heavy subunit of
human
ferritin was selectively expressed in dopaminergic neurons under the
control
of a
tyrosine hydroxylase promoter. Ferritin converts harmful ferrous iron
to
unreactive ferric iron (Fe3+), which it sequesters in large
quantities. The
presence
of ferritin greatly attenuated the loss of the vulnerable
dopaminergic
neurons in the substantia nigra, as assessed by stereological cell
counts of
tyrosine-hydroxylase-positive neurons seven days after MPTP
administration. It
also
led to partial reverses in the increase in reactive oxygen species
and
decreases in glutathione levels seen after MPTP administration,
changes which
are also
characteristic of Parkinson's disease brains.

A second iron-removing strategy -- dosing with the metal chelating
antibiotic
5-chloro-7-iodo-8-hydroxyquinoline (clioquinol) -- was also shown to
attenuate
the MPTP-induced cell loss and detrimental biochemical changes.
Clioquinol
chelates both ferrous and ferric iron and is already in Phase II
clinical
trials
for another neurodegenerative disease, Alzheimer's disease, in which
its
metal-chelating properties are thought to inhibit -amyloid
accumulation. In
this
study, clioquinol was shown to protect neurons after both acute and
chronic
(five day) MPTP insults. Both the ferritin-expressing and clioquinol-
treated
mice
were reported to show less decline in motor activity than normal
animals
following dosing with MPTP.

With the identification of ferrous iron as a causative element in the
pathological progression of Parkinson's disease, the search is on for
agents
that can
achieve the delicate balance of sequestering excess reactive iron in
vulnerable regions of the brain, without damaging the many systems
that rely
on normal
iron levels for their functioning.

References and links

ORIGINAL RESEARCH PAPER
Kaur, D. et al. Genetic or pharmacological iron chelation prevents
MPTP-induced neurotoxicity in vivo: a novel therapy for Parkinson's
disease.
Neuron 37,
899-909 (2003) | PubMed | ChemPort |

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(c) 2003 Nature Publishing Group

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"Iron is vital to human life; for example, it is a component of
hemoglobin, the substance that makes our blood red and supplies our
cells with oxygen. However, iron can also cause heavy damage; it is
thought that iron deposits in the brain contribute to certain forms of
neurodegenerative diseases such as Parkinsons's, Huntington' s, and
Alzheimer's. A malfunction of the blood transporter transferrin may be
to blame."

There you have it, a disorder in the normal finely tuned process of
controled iron levels is the cause, iron deposits is the effect.  This
comes on the heels of another posted article showing iron is the effect
and not the cause in cell aging.

Jesus ate a mediterranean diet.