The "pigmented" neurons of the substantia nigra
contain a polymer called "neuromelanin". It
is comprised of two "subunits", but these are
derived from dopaquinone, an auto-oxidation
byproduction of DOPAC (a dopamine metabolite).
Neuromelanin serves two purposes:
1) It acts as a sink for dopamine quinones,
which are dangerous to the cell because they
can act as...
a. alkylators (will bind to macromolecules)
b. redox cycling agents (which can
shift the pools of NADPH and reduced
glutathione to NADP and oxidized
glutathione; eventually depleting
the cellular pools of these chemicals).
2) It acts as a metal ion chelator (Fe, Cu,
Zn, etc...). These high-energy cells tend
to accumulate metals, which can be toxic.
An unfortunate byproducts of iron (Fe)
chelation are superoxides, since:
a. neuromelanin forms a standing free
radical, and...
b. will cycle iron between the +2
and +3 states.
Neuromelanin, in general , is considered to
be protective. It is assumed that nigral
dopaminergic neurons posess the ability
to form neuromelanin as a means of defense
against the cells own toxic metabolic byproducts.
Hope this info helps.
Michael L. Kirby
