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Pharmacological Management of Amyotrophic Lateral Sclerosis
Published in Sahab Uddin, Rashid Mamunur, Advances in Neuropharmacology, 2020
Shalini Mani, Chahat Kubba, Tanya Sharma, Manisha Singh
All of the aforementioned targets-excitotoxicity, protein cytoskeletal dysfunction neuroinflammation and glial activation, are not mutually exclusive but probably communicate with each other rather dynamically and may be mechanically cohesive either through involvement of a common origin in protein accumulation disorders or phenomenon of enhanced level of oxidative stress (Poon et al., 2005). For example, chief proteins including the tubulinbinding/stabilizing protein TCTP (translationally controlled tumor protein) and mutant SOD1 are both exceptionally carbonylated in the SOD1G93A spinal cord at later stages of disease (Poon et al., 2005). The protein deterioration system component ubiquitin carboxy-terminal hydrolase-L1 and alpha/beta-crystallinis are also evidently hypercarbonylated in this model animal (Poon et al., 2005). Therefore, expression of mutant SOD1 impacts the stability of protein by the process of enhanced carbonylation of protein; the oxidative impact might aggravate the pathways responsible for protein deterioration. The oxidative stress to cytoskeletal proteins might reduce the stress handling ability of the cells. The aggregates of post translationally modified proteins may enhance the activation of neuroinflammatory microglial cells.
Salivary microRNA as a prospective tool for concussion diagnosis and management: A scoping review
Published in Brain Injury, 2023
Thomas R. Campbell, Nicholas Reilly, Martina Zamponi, Delaney Leathers, Peter A. Mollica, Julie Cavallario, Jessica C. Martinez
Recently, research has focused on identifying biomarkers as an objective tool for diagnosing and managing concussions; such biomarkers include neuronal imaging, proteins, and metabolites (27). With the discovery of chronic traumatic encephalopathy (CTE) and the condition’s potential link to concussions, significant research over the past decade has focused on proteins such as Tau proteins, glial fibrillary acidic protein (GFAP), and ubiquitin carboxy-terminal hydrolase L1 (UCH-L1) as potential biomarkers of concussions (27,28). Although showing some promise, proteins are subject to degradation, making the identification of their presence often complex and highly time-sensitive. Additionally, they may require the disruption of an individual’s blood-brain barrier (BBB) to present in biofluids, making collection difficult, ultimately hindering their applicability (17,27,29–33). More recently, the use of microRNAs (miRNA) as an objective tool for diagnosing and managing concussions has also shown promise due to the ability to resist degradation, abundance, and stability despite fluctuating pH levels, and the role they play in the regulation of transcription. Furthermore, miRNAs play a significant role in neuronal injury and repair (27).
Glial fibrillary acidic protein as a biomarker in neuromyelitis optica spectrum disorder: a current review
Published in Expert Review of Clinical Immunology, 2023
Patrick Schindler, Orhan Aktas, Marius Ringelstein, Brigitte Wildemann, Sven Jarius, Friedemann Paul, Klemens Ruprecht
GFAP has previously been studied as a biomarker in several neurological disorders, most prominently in TBI, after which GFAP correlates with the extent of brain damage as assessed by cerebral computed tomography (CT) and magnetic resonance imaging (MRI) [82,85–88]. Indeed, the United States Food and Drug Administration (FDA) has approved a combined blood test for GFAP and ubiquitin carboxy-terminal hydrolase L1 (UCHL1) to predict the absence of intracranial lesions after mild TBI. Furthermore, GFAP has been shown to be elevated and to correlate with disease severity, at a varying degree, in MS and hemorrhagic and ischemic strokes, as well as several neurodegenerative disease entities [53,57,89]. The value of GFAP as a biomarker in these neurological disorders has been reviewed [53,90], with recent works focusing on GFAP in blood [57,89]. Very recently, elevated plasma GFAP levels have also been demonstrated in patients with COVID-19 encephalopathy as well as an association of a higher GFAP/NfL ratio with anxiety in post-COVID-19 patients [91].
Single-molecule measurements in microwells for clinical applications
Published in Critical Reviews in Clinical Laboratory Sciences, 2020
Connie Wu, Adam M. Maley, David R. Walt
Finally, single-molecule measurements have been used to measure blood-based biomarkers in traumatic brain injuries (TBI). Shahim and coworkers measured total tau by Simoa and S-100B and NSE by conventional ELISA in professional ice hockey players in Sweden to assess sports-related concussions [76]. Plasma and serum samples were collected from 47 players, 35 of whom suffered a concussion during the season. After a player suffered a concussion, blood was drawn at 1, 12, 36, and 144 h. The researchers reported significant increases in total tau (median 10 ng/L vs. 4.5 ng/L) and S-100B (median 0.075 µg/L vs. 0.045 µg/L) immediately after concussion. There was no significant increase in NSE compared to the preseason values. In addition to tau, NfL, GFAP, and ubiquitin carboxy-terminal hydrolase-L1 (UCH-L1) have also been measured in plasma as potential markers for TBI [77,78]. Gill and coworkers used Simoa to measure significantly elevated levels of tau, NfL, and GFAP in patients with suspected mild traumatic brain injury (mTBI) compared to healthy controls. Additionally, among patients with mTBI, plasma levels of tau, NfL, and GFAP were able to differentiate between patients with and without abnormalities in magnetic resonance imaging.