Textbook of Personalized Medicine - Second Edition [2015]

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Regeneration and Degeneration of the Nervous System Neuroproteomic tech-
nologies have been designed to uncover the mechanisms and molecules involved in
neuronal regeneration and degeneration (Sun and Cavalli 2010 ). Most proteins
mediating regeneration are found to be either malfunctioning or reduced in
degeneration.


Study of the Blood-Brain Barrier Proteomic technologies can be used to study
neuropathology at the blood-brain barrier (BBB). Proteomics can also be applied to
facilitate drug delivery across the BBB by characterizing active effl ux systems that
can prevent drug access to the brain and by identifying new transporters that could
be used as noninvasive drug delivery conduits.


Use of Neuroproteomics for Study of Neurologic Disorders Neuropathologies
involving loss of neurons and disturbances of neurotransmission may result in
disease- specifi c alterations of neuronal and CSF proteins that are suitable for pro-
teomics analysis. CNS proteomics may identify cell types and tissues contributing
to the disease phenotype. Proteomics analysis of human brain tissue has been done
as an extension of the study of CSF proteins. These studies are further facilitated by
the availability of 2D maps of brain-specifi c proteins. Role of neuroproteomics in
the management of individual disorders will be described in sections dealing with
these disorders.


CSF Tests Based on Proteomics


CSF examination provides a practical way to conduct longitudinal molecular analy-
ses of changes during the course of neurologic disease. Integrated and parallel anal-
yses of neurotransmitters, neuropeptides, and fi ngerprints of proteins in the CSF
may provide a better insight into underlying pathomechanisms. Proteomics investi-
gations of CSF have led to the discovery and validation of biomarkers, mainly in the
fi eld of neurodegenerative disorders (Gabelle et al. 2009 ). Some disease-specifi c
proteins identifi ed in the cerebrospinal fl uid of patients with neurologic disorders
are shown in Table 12.2.


Diagnosis of Neurologic Disorders by Examination


of Proteins in the Blood


S-100 Antibody-based tests can measure proteins in the blood. Concentrations of the
S-100 protein, an acidic calcium-binding protein found in the gray matter of the brain,
are elevated in serum after brain damage. Measurement of serum concentrations of
S-100 is a valuable tool that can be used more easily than tests on CSF in the differ-
ential diagnosis of Creutzfeldt-Jakob disease, as signifi cantly higher concentrations


12 Personalized Management of Neurological Disorders
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