Neuroproteomics and systems biology‐based discovery of protein biomarkers for traumatic brain injury and clinical validation

Abstract

The rapidly growing field of neuroproteomics has expanded to track global proteomic changes underlying various neurological conditions such as traumatic brain injury (TBI), stroke, and Alzheimer's disease. TBI remains a major health problem with approximately 2 million incidents occurring annually in the United States, yet no affective treatment is available despite several clinical trials. The absence of brain injury diagnostic biomarkers was identified as a significant road-block to therapeutic development for brain injury. Recently, the field of neuroproteomics has undertaken major advances in the area of neurotrauma research, where several candidate markers have been identified and are being evaluated for their efficacy as biological biomarkers in the field of TBI. One scope of this review is to evaluate the current status of TBI biomarker discovery using neuroproteomics techniques, and at what stage we are at in their clinical validation. In addition, we will discuss the need for strengthening the role of systems biology and its application to the field of neuroproteomics due to its integral role in establishing a comprehensive understanding of specific brain disorder and brain function in general. Finally, to achieve true clinical input of these neuroproteomic findings, these putative biomarkers should be validated using preclinical and clinical samples and linked to clinical diagnostic assays including ELISA or other high-throughput assays.

Blood biomarkers for evaluation of perinatal encephalopathy: state of the art

“…MAP2 is generally dendrite-specific and potentially a good candidate biomarker for dendritic injury (Kobeissy et al, 2008). A study of 16 patients with severe traumatic brain injury found that serum MAP2 concentrations correlated with neurologic outcome at 6 months after injury (Mondello et al, 2012c).…”

Immunohistochemical Correlation of Novel Biomarkers with Neurodegeneration in Rat Models of Brain Injury

“…4) with advances in molecular biology, specifically in proteomics (Kobeissy, Sadasivan et al 2008). Despite previous discoveries such as C-reactive protein and serum amyloid A, which are not very useful as biomarkers due to lack of specificity, some progress has been made by this approach (Dash, Zhao et al 2010).…”

“…Conversely C-reactive protein, transferrin, breakdown products of CRMP-2, synaptotagmin, and II-spectrin were found to be elevated after TBI . One of the novel biomarkers that increased was Ubiquitin C-terminal hydrolase-L1 (UCH-L1) (Kobeissy, Sadasivan et al 2008), also known as neuronal-specific protein gene product 9.5 (PGP9.5). UCH-L1 was previously used as a histologic marker for neurons because of its high abundance and specific expression in neurons (Fig.…”

Novel Strategies for Discovery, Validation and FDA Approval of Biomarkers for Acute and Chronic Brain Injury

“…In addition, genomics and proteomics are powerful, complementary tools that play an important role in the area of biomarker identification. Over the past few years, advances in the fields of neuroproteomics and neurogenomics have led to the discovery of many candidate biomarkers and are becoming the primary methods for initial candidate marker selection (Kobeissy et al 2008, Wang et al 2006, Nogoy 2007. The identification of differentially expressed candidate markers using these techniques is proving to be only the first step in the biomarker Novel Strategies for Discovery, Validation and FDA Approval of Biomarkers for Acute and Chronic Brain Injury 457 development process.…”