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Synapses
Published in Nassir H. Sabah, Neuromuscular Fundamentals, 2020
The phosphate group is hydrolyzed back to an OH– group by enzymes referred to as phosphatases, and the process is known as dephosphorylation. Protein phosphatase 1 (PP1) dephosphorylates a variety of proteins as well as K+ and Ca2+ channels, NMDA, and AMPA glutamate receptors. Protein phosphatase 2A (PP2A) also dephosphorylates a range of proteins that overlap with those of PP1, in addition to tau protein that stabilizes microtubules of the cytoskeleton. Excessive phosphorylation of tau protein is associated with Alzheimer’s disease. Protein phosphatase 2B (PP2B), also known as calcineurin, is abundant in neurons and is activated by Ca2+. It activates T cells of the immune system and dephosphorylates AMPA receptors. Protein phosphorylation and dephosphorylation are of fundamental importance in cell functioning as it is the major molecular mechanism through which protein activity in a cell is regulated both in and outside the nervous system.
Nanomedicine for the Treatment of Neurological Disorders
Published in Sarwar Beg, Mahfoozur Rahman, Md. Abul Barkat, Farhan J. Ahmad, Nanomedicine for the Treatment of Disease, 2019
Alzheimer’s is disease of aging brain which can be identified by the accumulation of amyloid-β plaques and neurofibrillary tangles of hyper-phosphorylated tau protein in the brain. AD people also show low level of acetylcholine and less activity of P-glycoprotein in their brain (Hartz et al., 2016; Nalivaeva et al., 2016). Although, AD has been studied for over a century now, still approved anti-AD therapeutics is unable to inhibit neurodegenerative process and, multifactorial pathogenesis of AD and limitation of drug transport due to brain barrier make it more difficult. Therefore, use of nanoparticle-based AD therapeutics has been increased from last few years.
Neuroprotective effect of peanut against oxidative stress in streptozotocin-induced diabetic rats
Published in Egyptian Journal of Basic and Applied Sciences, 2022
Norhan H. Mohamed, Hassan Elsayad, Yasser M. Elsherbini, Mohamed E. Abdraboh
The observed findings revealed that the diabetic-related inflammation led to injured brain structure and reduced brain function which were correlated with the significant upregulation of brain tau protein, amyloid-β and α-amylase. In diabetes, amyloid-β and tau proteins have been considered as the major components of senile plaques and neurofibrillary tangles, respectively. The hyperphosphorylation of tau protein would stimulate its aggregation to form neurofibrillary tangles [61]. The hippocampus of STZ-induced diabetic rats showed a significant increase in the levels of amyloid precursor protein (APP), amyloid-β expressions and phosphorylated tau [62,63]. The upregulation of brain α-amylase enzyme level in diabetic rats indicated their high susceptibility to neuronal damage which was reversed by peanut oral supplementation. These results were supported by other studies which revealed the role of altered levels of α-amylase in brains leading to variations of glucose readiness and neuropathological changes observed in patients with Alzheimer’s disease [64].
Investigating sensitivity coefficients characterizing the response of a model of tau protein transport in an axon to model parameters
Published in Computer Methods in Biomechanics and Biomedical Engineering, 2019
Ivan A. Kuznetsov, Andrey V. Kuznetsov
One of the hallmarks of Alzheimer’s disease (AD) is the formation of insoluble neurofibrillary tangles (NFTs) composed of tau protein (Ballatore et al. 2007; Tai et al. 2012; Ittner et al. 2011; Bloom 2014). Some recent research suggests that abnormalities in axonal transport precede NFT formation and any clinical symptoms of AD (Moreno et al. 2016). The relevance to AD explains the importance of understanding and modeling tau transport in neurons. This is especially important because tau and its interaction with microtubules (MTs) have been identified as a possible therapeutic target in AD (Boutajangout et al. 2011; Pachima et al. 2016; Lippens et al. 2016). For example, DeVos et al. (2017) presented evidence that tau reduction therapy can reverse tau seeding capability in aged mice with tauopathy.
Clinical translation of biomedical sensors for sports medicine
Published in Journal of Medical Engineering & Technology, 2019
Dhruv R. Seshadri, Samantha Magliato, James E. Voos, Colin Drummond
Between 1.6 and 3.8 million people are diagnosed with a sports or recreation-related brain injury in the United States annually [28]. The increasing prevalence of athletic-related concussions has instigated the need to both quickly and accurately diagnosis and manage concussions by medical personnel, team trainers, and sports teams. The NFL defines a concussion as a complex pathophysiological process affecting the brain induced by biomechanical forces [29,30]. A concussion is sustained when the brain, which essentially floats in the cerebrospinal fluid, collides with the inside of the skull due to an impact to the head or a whiplash motion. Concussions have become one a high priority in sports medicine because of the increased prevalence as well as the complex and ambiguous pathophysiology consequences of a concussion. Current goals of concussion research include decreasing the incidence of concussions, developing improved real time diagnosis methods, and identifying definitive biomarkers of concussions that allows for quantitative diagnoses [29]. Quanterix, a life science start-up, which manufactures devices to measure proteins and biomarkers in the blood, has garnered heightened attention by the NFL due to its work for searching for markers of concussions and neurodegenerative diseases [29]. The biosensor contains a single-molecule array containing millions of microscopic beads to detect proteins in blood. The beads are coated with antibodies and are submerged into fluid samples where they latch onto any target molecule that comes into contact with them. The captured molecules are tagged with an enzyme, analogous to an enzyme-linked immunosorbent assay, (ELISA), and are placed in a trigger fluid. The presence of the enzyme lights up the well, thereby detecting the target molecule. Based off this work, researchers from the University of Gothenburg showed increased levels of tau protein in the plasma of boxers following knockout [30]. Tau protein holds together the matrix that carries neurological signals between brain cells. During head impact collisions, tau proteins dislodge and cross the blood brain barrier and deteriorate thereby becoming P-Tau, the primary marker found in chronic traumatic encephalopathy (CTE), the progressive degeneration of the brain due to repeated trauma [31–33]. Inclusion of nanomaterials in biochemical sensors could be used to track or measure biomarkers or protein concentrations and could serve as the new gold standard for this field.