and one locus at the chromosome 22q12 indicates an increased risk for this type of
nephropathy.^131 Quantitative proteomic analysis of renal tissues^132 and analysis of
urinary exosomes of IgA nephropathy and thin basement membrane nephropathy
patients resulted in the identification of aminopeptidase N, vasorin precursor, alpha-
1-antitrypsin, and ceruloplasmin as potential biomarker candidates. Identification
of these relatively highly abundant proteins that are frequently present in patients
with proteinuria is not a spectacular result, but the use of urinary exosomes for
biomarker discovery is new and a highly promising strategy for future high-
throughput analyses in order to obtain results for use in patient personal care.^133
5.4 Neurodegenerative Diseases
The problem of neurodegenerative diseases is raising parallel with the raising of life
expectance and aging of the population in the Western world. The most common
age-related neurodegenerative diseases Alzheimer’s disease (AD), Huntington’s
disease (HD), and Parkinson’s disease (PD) are all associated with the accumu-
lation of misfolded proteins and their aggregation into microscopically visible
bodies. Some of these aggregates with fibrilar structures are discovered and character-
ized long time before the “omics” period. The heredity of these diseases was also
early recognized.^134 Misfolded proteins that are specific for each of the above-
mentioned degenerative disease are amiloid-beta and -tau in Alzheimer’s, super-
oxide dismutase in amyotropic lateral sclerosis, mutant huntingtin in Huntington’s,
and alpha-synuclein in Parkinson’s disease. The role of the aggregates is still not
totally clear, but it seems that they represent a kind of misled cellular protection
mechanism against toxic aggregation intermediates. Some inherited forms of neuro-
degenerative diseases often involve mutation of disease proteins that even increase
their misfolding and aggregation.^135 Huntingtin is the protein that forms aggregates
in Huntington’s disease. The aggregation is caused by expansion of a poly-
glutamine stretch within the amino-acid chain in the protein, and in this and other
diseases caused by similar mechanism, there is a direct correlation between the
length of the polyglutamine chain and the aggregation properties and toxicity of
disease proteins.^136 Not only misfolding properties of these proteins but also other
inherited factors play a key role in the development of these neurodegenerative
diseases.^137
(^131) Gharavi et al. ( 2011 ), pp. 321–327.
(^132) Sui et al. ( 2014 ), pp. 793–798.
(^133) Grollman et al. ( 2007 ), pp. 12129–12134.
(^134) Gusella et al. ( 1983 ), pp. 234–238.
(^135) van Ham et al. ( 2009 ), pp. 360–370.
(^136) Chen et al. ( 2002 ), pp. 11884–11889.
(^137) Rosenblatt et al. ( 2001 ), pp. 399–403.
202 D. Josic ́and U. Andjelkovic ́