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Studies conducted in the saliva of individuals with mild cognitive impair-

ment (MCI) and AD have also reported that salivary transthyretin (TTR),

cystatin-C, interleukin-1 receptor antagonist, stratifin, matrix metallopro-

teinase 9 and haptoglobin protein levels vary compared to controls [54, 55].

In general, various studies conducted by different researchers have shown

that serum, plasma, saliva and urine may also contain proteins that will pro-

vide information about disease pathogenesis [54–57]. However, these findings

in proteomic studies have not yet become biomarker panels that will support

clinical diagnosis due to the need for further validation in large samples.

10.6.2

Parkinson’s Disease (PD)

PD, considered the second most common neurodegenerative disease, is char-

acterized by the preferential degeneration of dopaminergic neurons extending

from the substantia nigra to the striatum. Motor dysfunctions that occur in

the middle and late stages of the disease are attributed to the loss of more than

half of these neurons. Dopaminergic neurons are cells rich in mitochondria to

meet high energy needs, and in many studies the pathogenesis of the disease

has been associated with mitochondrial dysfunction [58]. Proteomic studies

conducted with both human brain and model organisms have highlighted

proteins related to neuroinflammation, oxidative stress, and the Ubiquitin-

proteasome system, especially mitochondrial respiratory chain proteins. In

this context, the substantia nigra has been the most studied region of the

brain due to dopaminergic neuron losses [59–61]. The results of an in-depth

proteomic analysis, in which more than ten thousand proteins were identified,

also showed that the downregulated mitoribosome proteins in the substantia

nigra were the most dysregulated proteins [59]. In the study characterizing

the protein profile of synaptosomes isolated from neuronal cell bodies in this

region, it was pointed out that mitochondrial Thymidine kinase 2 (TK2), 39S

ribosomal protein L2, neurolysin and Methionine-tRNA ligase (MARS2) may

have a stronger relationship with Parkinson’s disease than known [61].

In addition to post-mortem brain tissue, the pathogenesis of the disease

has also been investigated in animal models developed with toxin treatments

that promote PD-like dopaminergic neuron loss. In some studies, proteomic,

targeted proteomic and phosphoproteomic analyses were performed on vari-

ous samples obtained from zebrafish that exhibited PD-like symptoms after

exposure to rotenone, a neurotoxin. Interestingly, in addition to mitochon-

drial proteins altered by rotenone toxicity, it has been reported that proteins

involved in the redox system, calcium and lipid transport activity, and energy

metabolism were significantly improved after octanoic acid and erucic acid

treatments [62–64].

On the other hand, biomarker studies have been conducted in various

biological fluids for Parkinson’s disease, as well as Alzheimer’s. In a CSF

proteomics study aiming to distinguish Parkinson’s syndromes from healthy

controls, 341 proteins were quantified using two different cohorts. Of the 13