oxidative modification of a large number of proteins. These results also indicate that
mitochondria are the organelles where these changes start.^146 Tau protein, espe-
cially its phosphorylated form, and the 42 amino-acid-containing peptide originated
from amyloid-beta identified in the cerebrospinal fluid are strong biomarker candi-
dates.^147 Thambisetty et al.^148 suggest complement components C3 and C3a,
complement factor-I, gamma-fibrinogen, and alpha-1-microglobulin as plasma bio-
markers for brain atrophy and Alzheimer’s disease. However, change in the con-
centration of these proteins with relatively high abundance occurs in a row of
pathological changes in an organism, e.g. in inflammation, and biomarkers like
proteins with lower abundance or with specific PTMs are recommended for early,
reliable, and fast diagnosis of this disease.
The genome-wide association study in a large group of Parkinson’s disease
affected persons and corresponding controls resulted in the observation of the
strong association signals in two genes—one that encodes the protein alpha-
synuclein and another at the MAPT locus.^149 Further genetic investigations resulted
in the identification of the prominent role of mitochondrial dysfunction and the
products of further disease-associated genes (reviewed by Henchcliffe and Beal^150 ).
These investigations confirm early finding about the role of the alpha-synuclein
gene in the etiology of this disease^151 and also result in further investigation about
the role of this protein in Parkinson’s disease, its aggregation,^152 interaction with
other proteins such as molecular chaperones (heat shock proteins), and possible
strategies for disease treatment that are based on this knowledge.^153 Proteomic
analyses of degenerating tissue substantia nigra yielded in the identification of
several mitochondrial proteins as candidate biomarkers and targets for treatment
of this disease.^154 In a rat model, as well as by analysis of human tissue, proteins
that are potentially involved in synaptic changes were identified.^155 Eller and
Williams^156 present the overview of results of high-throughput analyses of plasma,
urine, and cerebrospinal fluid as samples for the identification of biomarkers for
Parkinson’s disease and conclude that only in the cerebrospinal fluid both proteins
or protein fragments specific for disease process alpha-synuclein and tau fragments
could be identified. Following this recommendation, Lehnert et al.^157 use
(^146) Castegna et al. (2002a), pp. 562–571; Castegna et al. (2002b), pp. 1524–1532.
(^147) Blennov and Hampel ( 2003 ), pp. 605–613.
(^148) Thambisetty et al. ( 2011 ).
(^149) Simo ́n-Sa ́nchez et al. ( 2009 ), pp. 1308–1312.
(^150) Henchcliffe and Beal ( 2008 ), pp. 600–609.
(^151) Polymeropoulos et al. ( 1997 ), pp. 2045–2047.
(^152) Spienlli et al. ( 2014 ), pp. 2037–2050.
(^153) Jones et al. ( 2014 ), pp. 33–51.
(^154) Pienaar et al. ( 2010 ), pp. 205–226.
(^155) Xiong et al. ( 2014 ), pp. 1808–1819; Licker et al. ( 2014 ), pp. 784–794.
(^156) Eller and Williams ( 2009 ), pp. 561–570.
(^157) Jesse et al. ( 2012 ), pp. 99–505.
204 D. Josic ́and U. Andjelkovic ́