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Nutritional Interventions for the Prevention of Neurodegenerative Disorders *
Published in Abhai Kumar, Debasis Bagchi, Antioxidants and Functional Foods for Neurodegenerative Disorders, 2021
Pradipta Banerjee, Sayantan Maitra, Preetha Bhadra, Amitava Das, Nandini Ghosh, Sayantani Karmakar, Debasis Bagchi
Regular consumption of red meat (beef, pork, lamb) may be associated with many human diseases, such as chronic constipation, carcinomas, atherosclerotic cardiovascular disease, diabetes, and inflammatory diseases that may end up in NDDs. The red meat contains nonhuman sialic acid N-glycolylneuraminic acid (Neu5Gc), which is considered as “xenoautoantigen”; i.e., it can incorporate into human metabolic system and induce an immune response against self-antigens (Alisson-Silva et al., 2016). Neu5Gc incorporates in human tissues resulting in an interaction with inflammation-provoking antibodies against xenoautoantigens and ultimately leading to the early onset of NDDs. Besides red meat, high-fat diets are the causative agents for overproduction of the circulatory free fatty acids and systemic inflammation, and promote oxidative stress and neurodegeneration. Human brain is highly susceptible to oxidative stress as high amounts of unsaturated fatty acids and oxygen are present in brain. These unsaturated fatty acids and oxygen serve as the substrate for lipid peroxidation (Darmon et al., 2005), the products of which are the prominent biomarkers of oxidative stress in NDDs.
Fatigue in disease
Published in Francesco E. Marino, Human Fatigue, 2019
An enticing but speculative hypothesis is that diet is a significant factor in the development of neurological pathology. For example, since MS seems to develop exclusively in humans it is hypothesised that non-human primates are resistant against MS but susceptible to the MS animal model, known as experimental autoimmune encephalomyelitis (EAE) (‘t Hart 2016). These authors suggest that an important difference between human and non-human primates is that humans are unable to synthesise the sialic acid N-glycolylneuraminic acid (Neu5Gc). As such they propose that long-term ingestion of red meat increases the foreign Neu5Gc, which is introduced into vital regions of the central nervous system, such as the blood-brain barrier (BBB) and the axon-myelin unit. This potentiates binding of de novo synthesised heterophilic anti-NeuGc antibodies, causing blood-brain barrier leakage and destabilisation of axon-myelin coupling, which could initiate the characteristic pathological features of MS. This hypothesis does not auger well if we accept that Homo developed a propensity for meat eating as a way to fuel the development and maintenance of the large brain. In addition, the fact that these pathologies restrict the development of high muscular forces suggests that at a systemic level fatigue might have been much more debilitating if strength and power were selected because larger myelinated fibres are less fatigue resistant.
Structure, heterogeneity and developability assessment of therapeutic antibodies
Published in mAbs, 2019
Yingda Xu, Dongdong Wang, Bruce Mason, Tony Rossomando, Ning Li, Dingjiang Liu, Jason K Cheung, Wei Xu, Smita Raghava, Amit Katiyar, Christine Nowak, Tao Xiang, Diane D. Dong, Joanne Sun, Alain Beck, Hongcheng Liu
It is not uncommon for mAbs to have a consensus sequence for N-glycosylation (NXS/T, X cannot be P) in variable domains, in addition to the conserved N-glycosylation site in the Fc region. The variable domain glycosylation showed variable effects on antigen binding,64-69 but no impact for in vivo half-life.67,70 Variable domain glycosylation adds another level of uncertainty with regard to potency and comparability later in development. The higher level of terminal galactose of Fab glycosylation increases the likelihood for further galactosylation by α1,3-galactose and sialylation. Fab-associated oligosaccharides with the addition of α1,3-galactose (Gal) have been shown to cause immunogenicity.71 Sialylation could also add the immunogenic moiety of N-glycolylneuraminic acid (NGNA).12,72 It is worth mentioning that the addition of α-1,3Gal and NGNA is highly dependent on cell line,12,13,72 and their levels should be evaluated using material from the intended stable cell line.
Antibodies against aberrant glycans as cancer biomarkers
Published in Expert Review of Molecular Diagnostics, 2019
Anna Blsakova, Filip Kveton, Peter Kasak, Jan Tkac
N-acetylneuraminic acid (Neu5Ac) and its hydroxylated form N-glycolylneuraminic acid (Neu5Gc) are two main forms of sialic acid present in mammals (Figure 4) [84,85]. Neu5Gc is not naturally synthetized in humans due to absence of the hydroxylase converting Neu5Ac to Neu5Gc [84,85]. Due to Neu5Gc intake by eating of red meat of a mammalian origin, Neu5Gc (a xeno-autoantigen) is incorporated into human tissues eliciting an immune system with production of anti-Neu5Gc Abs [84,85]. The resulting chronic inflammation or ‘xenosialitis’ can progress into various diseases including cancer, type 2 diabetes and atherosclerosis [85,86]. Anti-Neu5Gc Abs might have potential application in cancer immunotherapy and also as cancer biomarkers [85].
Glycoform-resolved pharmacokinetic studies in a rat model employing glycoengineered variants of a therapeutic monoclonal antibody
Published in mAbs, 2021
David Falck, Marco Thomann, Martin Lechmann, Carolien A. M. Koeleman, Sebastian Malik, Cordula Jany, Manfred Wuhrer, Dietmar Reusch
Immunogenic glycoforms, such as N-glycolylneuraminic acid or α1,3-linked galactose, may increase the immunogenicity risk, and consequently lead to hypersensitivity reactions.13 Since mannose receptor is also involved in antigen presentation, the chance for anti-drug antibodies might be greater when the mAb is cleared via mannose receptor.9,10