The substantia nigra is a good target to study the effects of
oxidative stress because it is loaded with mitochondria and has heavy
oxidative metabolism due to the Dopamine production.  Also the
Parkinson disease is a phenotypical demonstration of the pathology.
Now what mitochondria need for their oxidative metabolism - it's the
Iron (dark brown color, nigra, like in the brown fat of babies which
use the mitochondria to heat them up) .. so iron is essential.  What
is not essential are the highly unsaturated PUFAs of the Omega-3 and
Omega-6 series because they oxidize easily to reactive lipid peroxides
causing all the havoc including large deletions in mtDNA (the "common
deletion") which in turn lead to elevated ROS/RNS production due to
the clonal expansion of the defective ROS-overproducing mitochondria.
In another tissue this would result in cancer.  You can possibly kill
(autophage) the defective mitochondria by CR/ketosis otherwise they
will just expand on high carb/insulin/TOR diet.  But if you store a
lot of Omega-6 in the adipose tissue the CR may kill you due to its
release upon starvation.

Taka

J Neurochem. 2003 May;85(3):645-50.

Isofurans, but not F2-isoprostanes, are increased in the substantia
nigra of patients with Parkinson's disease and with dementia with Lewy
body disease.

Fessel JP, Hulette C, Powell S, Roberts LJ 2nd, Zhang J.
Department of Pharmacology, Vanderbilt University Medical Center,
Nashville, Tennessee, USA.

F2-isoprostanes (F2-IsoPs) are well-established sensitive and specific
markers of oxidative stress in vivo. Isofurans (IsoFs) are also
products of lipid peroxidation, but in contrast to F2-IsoPs, their
formation is favored when oxygen tension is increased in vitro or in
vivo. Mitochondrial dysfunction in Parkinson's disease (PD) may not
only lead to oxidative damage to brain tissue but also potentially
result in increased intracellular oxygen tension, thereby influencing
relative concentrations of F2-IsoPs and IsoFs. In this study, we
attempted to compare the levels of F2-IsoPs and IsoFs esterified in
phospholipids in the substantia nigra (SN) from patients with PD to
those of age-matched controls as well as patients with other
neurodegenerative diseases, including dementia with Lewy body disease
(DLB), multiple system atrophy (MSA), and Alzheimer's disease (AD).
The results demonstrated that IsoFs but not F2-IsoPs in the SN of
patients with PD and DLB were significantly higher than those of
controls. Levels of IsoFs and F2-IsoPs in the SN of patients with MSA
and AD were indistinguishable from those of age-matched controls. This
preferential increase in IsoFs in the SN of patients with PD or DLB
not only indicates a unique mode of oxidant injury in these two
diseases but also suggests different underlying mechanisms of
dopaminergic neurodegeneration in PD and DLB from those of MSA.
PMID: 12694390

J Neuropathol Exp Neurol. 2002 Jul;61(7):634-9.

Mitochondrial DNA deletions/rearrangements in parkinson disease and
related neurodegenerative disorders.

Gu G, Reyes PE, Golden GT, Woltjer RL, Hulette C, Montine TJ, Zhang J.
Department of Pathology, Vanderbilt University Medical Center,
Nashville, Tennessee 37232-2561, USA.

Inhibition of mitochondrial respiratory chain function may contribute
to dopaminergic neurodegeneration in the substantia nigra (SN) of
patients with Parkinson disease (PD). Since large-scale structural
changes (e.g. deletions and rearrangements in mitochondrial DNA
[mtDNA]) have been associated with mitochondrial dysfunction, we
tested the hypothesis that increased total mtDNA deletions/
rearrangements are associated with neurodegeneration in PD. This study
employed a well-established technique, long-extension polymerase chain
reaction (LX-PCR), to detect the multiple mtDNA deletions/
rearrangements in the SN of patients with PD, multiple system atrophy
(MSA), dementia with Lewy bodies (DLB), Alzheimer disease (AD), and
age-matched controls. We also compared the total mtDNA deletions/
rearrangements in different brain regions of PD patients. The results
demonstrated that both the number and variety of mtDNA deletions/
rearrangements were selectively increased in the SN of PD patients
compared to patients with other movement disorders as well as patients
with AD and age-matched controls. In addition, increased mtDNA
deletions/rearrangements were observed in other brain regions in PD
patients, indicating that mitochondrial dysfunction is not just
limited to the SN of PD patients. These data suggest that accumulation
of total mtDNA deletions/rearrangements is a relatively specific
characteristic of PD and may be one of the contributing factors
leading to mitochondrial dysfunction and neurodegeneration in PD.
PMID: 12125742