China
Africa
Explore chapters and articles related to this topic
Phytochemicals' Potential to Reverse the Process of Neurodegeneration
Published in Meenu Gupta, Gopal Chaudhary, Victor Hugo C. de Albuquerque, Smart Healthcare Monitoring Using IoT with 5G, 2021
Surekha Manhas, Zaved Ahmed Khan
Neurons contain tau proteins that play a vital role in the stabilization of microtubules, to maintain cellular morphology and axonal transport [38]. The aggregation and accumulation of tau proteins in the form of neurofibrillary tangles leads to the neurodegeneration [39]. Tau protein loses its normal function when the paired helical filament undergoes hyper-phosphorylation that badly affects the frontotemporal lobe due to neuronal damage [40]. Interestingly, advanced researchers have demonstrated that a high dose of antioxidants decreases the tau hyperphosphorylation [41]. It has been observed that DNA damage increases in double in the neuronal cells in the case of AD patient than normal individuals, and it might be an earlier sign of disease that can be used as a biomarker for further studies [42]. The formation of neuritic plaques in the brain is considered a potent sign of developing disease [43].
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.
*
Published in Chad A. Mirkin, Spherical Nucleic Acids, 2020
Dimitra G. Georganopoulou, Lei Chang, Jwa-Min Nam, C. Shad Thaxton, Elliott J. Mufson, William L. Klein, Chad A. Mirkina
Alzheimer’s disease (AD) is the most common neurodegenerative dementia with an average death prognosis of 9 years [1]. There is no definitive diagnosis of the disease other than postmortem identification of senile plaques and neurofibrillary tangles in the brain [2, 3]. Premortem diagnosis, based on a patient’s clinical history; in vivo brain imaging [4–7]; and neuropsychological, cognitive, and neurological tests, is only ~85% accurate [8]. There are two general approaches for detecting soluble markers for AD. One approach is based on measuring the total tau protein or amyloid protein concentration in cerebrospinal fluid (CSF) or plasma [9–12]. This approach is hampered by significant overlap of such marker levels in healthy and unhealthy subjects and has led to inconclusive results [13–16]. The other approach targets only the suspected pathogenic markers, such as cleaved tau protein, phosphorylated tau protein [17], or amyloid-ß-derived diffusible ligands (ADDLs). Although this approach to detecting pathogenic markers might lead to more definitive results, the concentrations of such markers in CSF are so low in the early stages of the disease that they cannot be identified accurately with conventional ELISA or blotting assays. Here, we demonstrate that the ultrasensitive nanoparticle-based bio-barcode assay can be used to determine the approximate ADDL concentration in CSF taken from 30 subjects, 15 of whom were diagnosed with the disease through postmortem analysis of the brain and 15 of whom were found not to have the disease.
Why slow axonal transport is bidirectional – can axonal transport of tau protein rely only on motor-driven anterograde transport?
Published in Computer Methods in Biomechanics and Biomedical Engineering, 2023
Ivan A. Kuznetsov, Andrey V. Kuznetsov
Tau is mostly known for its involvement in Alzheimer’s disease and other tauopathies when it becomes prone to aggregation (Huang et al. 2016; Iqbal et al. 2010; Zempel and Mandelkow 2014; Blennow et al. 2006). In axons, tau is transported by SCb (Utton et al. 2002; Utton et al. 2005; Brown 2014). In this paper, we analysed equations from the model developed in Kuznetsov and Kuznetsov (2017a, 2018, 2020) to investigate what happens when all other modes of transport except kinesin-driven transport of tau become negligible. Our goal was to continue research reported in Kuznetsov and Kuznetsov (2022, 2023a) for α-synuclein, as well as in Kuznetsov and Kuznetsov (2023b) for MAP1B, and to determine whether anterograde motor-driven transport alone can replicate the tau distribution observed in experiments reported by Black et al. (1996). Focusing on scenarios where the dynein velocity and tau diffusivity were both small, we were able to derive an analytical solution for the tau transport model using the perturbation technique. This closed-form solution can be useful for verifying the accuracy of numerical codes.
The cushioning function of woodpecker’s jaw apparatus during the pecking process
Published in Computer Methods in Biomechanics and Biomedical Engineering, 2021
Peng Xu, Yikun Ni, Shan Lu, Sijian Liu, Xue Zhou, Yubo Fan
Woodpeckers have long attracted interest for their remarkable impact resistant abilities. Woodpeckers, which drummed and drilled with approximately 6–7 m/s and withstood the deceleration exceeding 1200 g, seem without any damage to its brain and eyes (May et al. 1976, 1979; Lu et al. 2020). Tau is a microtubule-associated protein in the central nervous system, and the hyperphosphorylation of tau will cause its accumulations and the loss of its physiological function. Tau accumulations usually are observed in association with chronic traumatic encephalopathy (CTE) and Alzheimer’s disease (AD) in humans. But Tau accumulations were found in the brain of woodpeckers recently (Farah et al. 2018). The impact-resistant performance of woodpecker’s head was questioned (Smoliga 2018), because CTE is a form of neurodegeneration disorder triggered by repetitive mild traumatic brain injury (mTBI). However, due to the differences in nervous systems between human and avian, it’s still unknown that these tau deposits are pathological or not (Farah et al. 2018; Smoliga 2018). What’s more, the impact-resistant mechanism of woodpeckers could be applied not only to prevent human’s traumatic brain injury (TBI) but also to develop bio-inspired structure and material for energy-absorbing (Bian and Jing 2014; Lee et al. 2016; Ni et al. 2017; Sabah et al. 2017; San Ha et al. 2019). Therefore, it is still meaningful to continue the study of woodpecker’s impact-resistant mechanism.
Subtle voices, distant futures: a critical look at conditions for patient involvement in Alzheimer’s biomarker research and beyond
Published in Journal of Responsible Innovation, 2020
Karen Dam Nielsen, Marianne Boenink
In the Dutch context, an extensive funding program was lauched in 2013 (ZonMW 2013). One of the research areas supported is biomarker research, aiming at measuring disease-related bodily parameters. While AD biomarkers are still far from standard clinical tools, the expectation put forward by funding agencies and involved researchers is that, at some point, they will be widely available and significantly improve, first of all, diagnostic certainty and precision and, further, contribute to prediction, improved prognosis, and development of drugs (Jack et al. 2011; Sun et al. 2018). Tau PET is one such envisioned biomarker for AD. It rests on the theory that cognitive decline due to AD is closely linked to the formation of tangles of the protein tau in the brain – whether this link is causal or merely a correlation (Jack et al. 2018). Until recently, tau tangles could only be observed post mortem through brain microscopy, yet the development of specific radioactive tracers has made it possible to visualize tau in the brains of living persons with PET scanning. This method enables researchers to investigate the presumed link between the presence of tau tangles in certain areas and AD symptoms (Aschenbrenner et al. 2018; Okamura et al. 2018). Researchers involved in the field often frame tau PET-imaging as ‘the new frontier’ in AD research, breaking with (or supplementing) years in which AD researchers mainly focused on plaques of the protein amyloid. Yet, at the beginning of our study, tau-PET research was generally perceived as still in its very early phase (Villemagne et al. 2015).