416
Small infarcts and transient ischemic attacks elevate only neuron-specifi c enolase.
Peak levels of both neuron-specifi c enolase and S-100 are statistically signifi cant
and correlate with clinical measures of stroke size and outcome.
Myelin Basic Protein This is localized in the myelin sheath and constitutes
approximately one third of the total protein of myelin from the human brain. Various
studies have indicated that myelin basic protein concentrations in plasma and serum
can be used as biomarkers for brain damage and severity of stroke. The increase of
myelin basic protein in cerebral infraction is most evident several days after the
onset, whereas in cerebral hemorrhage, the peak increase occurs almost immedi-
ately after the onset.
Transthyretin This is a protein biomarker that extravasates into the blood from the
CSF only if there is disruption of the CSF-blood barrier. Transthyretin can be
detected in the blood by proteomics technologies and is potentially useful for the
diagnosis of diseases where the CSF-blood barrier is disrupted.
Role of Proteomics in Neuropharmacology
An insight into protein-based mechanisms of neurologic disorders will provide
more relevant targets for drug discovery for CNS disorders. Neurodegenerative dis-
eases with underlying protein abnormalities are shown in Table 12.3.
Neuroproteomics studies show that neurodegenerative diseases share many
common molecular mechanisms, including misfolding of proteins. Further
understanding of these mechanisms may lead to strategies for prevention of neuro-
degenerative diseases and to the development of effective drugs. Identifi cation of
neurodegeneration- associated changes in protein expression will facilitate the iden-
tifi cation of novel biomarkers for the early detection of neurodegenerative diseases
and targets for therapeutic intervention. Applications of proteomics technologies
will facilitate a more comprehensive analysis of novel therapeutic strategies for
CNS disorders. This will also accelerate development of specifi c diagnostic and
prognostic disease biomarkers.
Table 12.3 Neurodegenerative diseases with underlying protein abnormalitiesDisease Proteins involved Inclusion bodies
Familial encephalopathy with myoclonus Neuroserpin Collin body
Familial Parkinson disease with Lewy bodies Alpha-synuclein Lewy body
Creutzfeldt-Jakob disease Prion protein vCJD amyloid
Alzheimer disease β-amyloid peptide β-amyloid plaques
Cofi lin inclusions
Pick disease Tau protein Pick body
Huntington disease Soluble huntingtin Insoluble huntingtin
GM1 gangliosidosis Defi ciency of β-gal GM1-ganglioside
© Jain PharmaBiotech
12 Personalized Management of Neurological Disorders