413Targeting the complete mitochondrial exome provides a greater potential to
identify rare variants that disrupt normal mitochondrial function, enabling an exact
diagnosis in a large proportion of patients that remain undiagnosed by other meth-
ods. Over 95 % of the target bases can be sequenced to an average coverage of
400×, providing highly accurate and sensitive results.
Neuroproteomics
The role of proteomics in personalized medicine has been described in Chap. 6.
Neuroproteomics is the term used for application of proteomics to the study of the
nervous system and its disorders with the aim of developing diagnostics and thera-
peutics (Jain 2002 ). Proteomics tools offer new ways to analyze networks of pro-
teins that control important neurobiological phenomena. Neuroproteomics,
combined with bioinformatics, can be used to study the organization of functional
protein networks and molecular structures that underlie physiological, anatomical,
and behavioral processes (Bayés and Grant 2009 ).
Applications of Neuroproteomics for Study of the Nervous System
Proteomics technologies are used for the study of neurotransmitters and neuronal
receptors. A brief description of these is as follows (Jain 2013 ):
Neurotransmitters Capillary electrophoresis has been combined with highly sen-
sitive micro-electrospray-tandem mass spectrometry to simultaneously detect classi-
cal small molecule neurotransmitters as well as neuropeptides from discrete regions
of the brain. Endogenous glutamate, gamma-aminobutyric acid, acetylcholine, and
dopamine as well as the neuropeptides methionine-enkephalin and substance P 1–7
could be detected in the striatum using only a minute amount of brain tissue. A dis-
ease-specifi c quantitative analysis of a specifi c neurotransmitter of interest may
require stabilization by inactivation of the degrading enzymes present in the CSF.
N-methyl-D-aspartate (NMDA) Receptors This is one of the ~100 neuronal
receptors known in humans. Proteomics technologies, such as mass spectrometry,
can be used to characterize multiprotein complexes of NMDA receptors, which are
encoded by activity-dependent genes.
Neuroprotection Use of neuroproteomics, systems biology, and bioinformatics
aim to study and establish a global assessment of the entire neuronal proteome
(Raad et al. 2012 ). Neuroproteomics aids in the understanding of molecular mecha-
nisms of neurogenesis. Potential neuroprotective pharmacological strategies can be
targeted at Rho and Rho kinases, which constitute key integral points in the pathway
that is known to be disrupted in multiple neuropathologies, such as spinal cord
injury and traumatic brain injury (Jain 2011 ).
Neuroproteomics