quantitative proteomics for the analysis of cerebrospinal fluid of Parkinson’s
patients and healthy controls. They recommend two proteins, tyrosine-kinase
nonreceptor type 13 and netrin G1, as candidate biomarkers for the development
of Parkinson’s disease dementia (see also Nature Rev. Neurology 8, doi:10.1038/
nrneurol.2012.34).
More than 30 years ago, Gusella at al.^158 demonstrated by use of recombinant
technology that a polymorphic DNA marker at the human chromosome 4 is genet-
ically linked to Huntington’s disease. Further investigations resulted in the identi-
fication of the corresponding gene and thorough genetic characterization.^159
Borovecki et al.^160 identified changes in patient’s blood mRNA that possibly reflect
mechanisms of disease observed in affected brain. They conclude that the alter-
nations in isolated mRNA may provide clues to the disease state and may also be
used as theranostic biomarkers for clinical trials and future disease treatment. In
proteomic profiling of plasma and cerebrospinal fluids of patient’s and control
individuals, Dalrymple et al.^161 identified some differently expressed proteins.
However, they are also typical biomarkers for neuroinflammation, and they con-
clude that not only the use of blood tests but rather the combination of several
clinical, neuroimaging, and biochemical biomarkers can be recommended to track
Huntington’s disease progression. By use of cultured human embryonic stem cells,
McQuade et al.^162 investigated proteomic changes as a consequence of pathology,
mitochondrial dysfunction, and metabolic disturbances as a consequence of this
disease. A shift of transcriptional dysregulation and cytoskeletal abnormalities were
identified as the primary pathologies. This shift was concomitant with an up-
regulation in expression of Huntington protein. This model can be used for the
studying of disease development and pathology and for “in vitro” investigation of
potential diagnostic and therapeutic use.
5.5 Diabetes Mellitus
Diabetes mellitus (DM) is a chronic disease caused by inherited and/or acquired
deficiency in the production of insulin by the pancreasβ-cells (T1DM) or by the
ineffectiveness of the insulin produced (T2DM). Such a deficiency results in
increased concentrations of glucose in the blood, which in turn damage many of
the body’s systems, in particular renal, retinal, neurological, or blood vessel dam-
age (WHO). The initial mechanism(s) behind the development of T1DM are largely
unknown. Proteins are involved in most cellular processes, and it is thus expected
(^158) Zhang et al. ( 2008 ), pp. 923–932.
(^159) The Huntington’s Disease Collaborative Group ( 1993 ), pp. 971–983.
(^160) Boroveck et al. ( 2005 ), pp. 11023–11028.
(^161) Dalrymple et al. ( 2007 ), pp. 2833–2840.
(^162) McQuade et al. ( 2014 ), pp. 5648–5659.
The Role of Proteomics in Personalized Medicine 205