Clinical utility of degradomics as predictors of complications and clinical outcome in aneurysmal subarachnoid hemorrhage

Abstract

Most of the debilitating conditions following aneurysmal subarachnoid hemorrhage result from symptomatic cerebral vasospasm and delayed cerebral ischemia. Several scales are being used, but they still lack objectivity and fail to quantify complications considered essential for prognostication routine use of biomarkers to predict complications and outcomes after aneurysmal rupture is still experimental. Degradomics were studied extensively in traumatic brain injury, but there is no discussion of these biomarkers related to aneurysmal subarachnoid hemorrhage. Degradomics involve the activation of proteases that target specific substrates and generate specific protein fragments called degradomes. While the proteolytic activities constitute the pillar of development, growth, and regeneration of tissues, dysregulated proteolysis resulting from pathological conditions like aneurysmal subarachnoid hemorrhage ends up in apoptotic processes and necrosis. To our knowledge, this is the first overview that lists a panel of degradomics with cut-off values in serum and cerebrospinal fluid, where specificity and sensitivity are only found in Kallikrein 6, Ubiquitin C Terminal Hydrolase 1 and Alpha-II-Spectrin.

Comparative analysis of aneurysm subtypes associated genes based on protein–protein interaction network

“…Result suggests a general role of ubiquitination associated pathways, including ubiquitin protein binding activity and ubiquitin-like protein binding activity, in all 6 studied subtypes. Through literature survey, we found that involvement of ubiquitination relevant pathways in aneurysm pathogenesis has been reported before in ASH, AAA, CA, AA and AD [ 15 – 21 ]. Thus, it is highly possible that ubiquitination extensively participates in progress of different aneurysmal diseases, through regulation of vascular inflammation and VSMCs phenotypic changes.…”

“…Through literature searches we found that the participant of ubiquitination related proteins (e.g. UCHL1, RNF213, UBR3, ARIH1) in pathogenesis of above-mentioned human aneurysm subtypes (ASH, AAA, CA, AA, AD) has been widely reported before [ 15 – 21 ]. As we already know, the ubiquitin-proteasome system (UPS) is a critical pathway in eukaryotic cells which functions through degrading cytosolic and nuclear proteins.…”

Deficiency in Androgen Receptor Aggravates Traumatic Brain Injury-Induced Pathophysiology and Motor Deficits in Mice

“…Glial fibrillary acidic protein (GFAP) is abundant in astrocytes and is necessary for CNS integrity and maintenance. A recent analysis of clinical reports has suggested that serum GFAP can be a useful tool to assess the clinical outcomes of patients with aneurysmal subarachnoid hemorrhage (SAH) [14]. GFAP is also a substrate of calpain-II protease and a widely used biomarker of astrogliosis in TBI [15].…”

“…In addition, alpha-II-spectrin, a neuronal scaffolding protein, is also a substrate of calpain II [16]. In particular, a recent clinical study reported correlation of alpha-II-spectrin breakdown product (SBDP) level with the clinical outcome and severity in patients with aneurysmal SAH [14]. Accumulation of breakdown products (BDPs) from GFAP and alpha-II-spectrin cleaved by calpain-II has been identified in the cerebrospinal fluid (CSF) after TBI [17].…”