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Progress in Molecular Biology and Translational Science

Ronald L Schnaar, Pablo H H Lopez
No abstract text is available yet for this article.
2018: Progress in Molecular Biology and Translational Science
Sandro Sonnino, Elena Chiricozzi, Sara Grassi, Laura Mauri, Simona Prioni, Alessandro Prinetti
Since the structure of GM1 was elucidated 55years ago, researchers have been attracted by the sialylated glycans of gangliosides. Gangliosides head groups, protruding toward the extracellular space, significantly contribute to the cell glycocalyx; and in certain cells, such as neurons, are major determinants of the features of the cell surface. Expression of glycosyltransferases involved in the de novo biosynthesis of gangliosides is tightly regulated along cell differentiation and activation, and is regarded as the main metabolic mechanism responsible for the acquisition of cell-specific ganglioside patterns...
2018: Progress in Molecular Biology and Translational Science
T August Li, Ronald L Schnaar
Gangliosides are expressed on all vertebrate cells and tissues, but are particularly abundant in the mammalian brain, where they constitute major cell-surface determinants on all nerve cells. The same four ganglioside structures, GM1, GD1a, GD1b, and GT1b, constitute the great majority of brain gangliosides in all mammals. Biosynthesis of these major brain gangliosides starts with addition of glucose to the ceramide lipid carrier followed by stepwise addition of up to six additional monosaccharides. This primarily involves the sequential action of seven glycosyltransferases, many of which appear to act specifically on glycolipid (rather than glycoprotein) acceptors...
2018: Progress in Molecular Biology and Translational Science
Robert W Ledeen, Gusheng Wu
This review addresses the role of α-synuclein (αSyn) in the etiopathology of Parkinson's disease (PD), with emphasis on its interaction with GM1 ganglioside. We begin with a brief review of some of the milestone discoveries that helped to elucidate PD neuropathology, including the fibrous inclusions of Lewy that characterize the degenerating dopaminergic neurons of the substantia nigra and the presence of αSyn as a major constituent of these Lewy bodies and neurites. This enabled Braak et al. to define the progressive nature of PD in developing their staging hypothesis which described the topographically predictable sequence of neuropathological changes giving rise to prodromal nonmotor symptoms that precede the classical motor dysfunctions...
2018: Progress in Molecular Biology and Translational Science
Katsumi Matsuzaki, Koichi Kato, Katsuhiko Yanagisawa
Assembly and deposition of amyloid β-protein (Aβ) is an early and invariable pathological event of Alzheimer's disease (AD), a chronic neurodegenerative disease affecting the neurons in the brain of aging population. Thus, clarification of the molecular mechanism underlying Aβ assembly is crucial not only for understanding the pathogenesis of AD, but also for developing disease-modifying remedies. In 1995, ganglioside-bound Aβ (GAβ), with unique molecular characteristics, including its altered immunoreactivity and its conspicuous ability to accelerate Aβ assembly, was discovered in an autopsied brain showing early pathological changes of AD...
2018: Progress in Molecular Biology and Translational Science
Pablo H H Lopez, Bárbara Beatriz Báez
Gangliosides are a family of sialic acid-containing glycosphingolipids highly expressed in the nervous system of vertebrates. Over the last 25years, research has unmasked several of their neurobiological functions but the role of gangliosides in the nervous system remains not fully elucidated. Genetic disruption of genes for key enzymes involved in ganglioside biosynthesis led to the discovery of their diverse functions and highlighted the exquisite structural specificity required in this processes. In the nervous system, gangliosides regulate axonal caliber and organize ion channels at the nodes of Ranvier, a critical step to ensure fast conduction velocity of myelinated fibers...
2018: Progress in Molecular Biology and Translational Science
John A Goodfellow, Hugh J Willison
A wide range of neuroimmunological diseases, referred to as autoimmune neuropathies, affect the peripheral nervous systems (PNS). The PNS is structurally diverse with complex anatomical compartments enriched in many different myelin and neuronal glycolipids, notably gangliosides. Autoimmune neuropathies are a proportion of autoimmune neuropathies mediated by autoimmune attack due to antibodies reactive with these compartmentally localized gangliosides. Antiganglioside antibodies are principally associated with the acute paralytic disease, Guillain-Barré syndrome, and are also found in several chronic autoimmune neuropathy syndromes...
2018: Progress in Molecular Biology and Translational Science
Madison Zuverink, Joseph T Barbieri
Subsets of protein toxins utilize gangliosides as host receptors. Gangliosides are preferred receptors due to their extracellular localization on the eukaryotic cell and due to their essential nature in host physiology. Glycosphingolipids, including gangliosides, are mediators of signal transduction within and between eukaryotic cells. Protein toxins possess AB structure-function organization, where the A domain encodes a catalytic function for the posttranslational modification of a host macromolecule, including proteins and nucleic acids, and a B domain, which encodes host receptor recognition, including proteins and glycosphingolipids, alone or in combination...
2018: Progress in Molecular Biology and Translational Science
Robert W Ledeen, Jürgen Kopitz, José Abad-Rodríguez, Hans-Joachim Gabius
Molecular signals on the cell surface are responsible for adhesion and communication. Of relevance in this respect, their chemical properties endow carbohydrates with the capacity to store a maximum of information in a minimum of space. One way to present glycans on the cell surface is their covalent conjugation to a ceramide anchor. Among the resulting glycosphingolipids, gangliosides are special due to the presence of at least one sialic acid in the glycan chains. Their spatial accessibility and the dynamic regulation of their profile are factors that argue in favor of a role of glycans of gangliosides as ligands (counterreceptors) for carbohydrate-binding proteins (lectins)...
2018: Progress in Molecular Biology and Translational Science
Koichi Furukawa, Yuhsuke Ohmi, Orie Tajima, Yuki Ohkawa, Yuji Kondo, Ji Shuting, Noboru Hashimoto, Keiko Furukawa
Gangliosides play roles in the regulation of cell signaling that are mediated via membrane microdomains, lipid rafts. In this review, functions of gangliosides in the maintenance of nervous systems with a focus on regulation of inflammation and neurodegeneration are addressed. During analyses of various ganglioside-lacking mutant mice, we demonstrated that nervous tissues exhibited inflammatory reactions and subsequent neurodegeneration. Among inflammation-related genes, factors of the complement system showed up-regulation with aging...
2018: Progress in Molecular Biology and Translational Science
Yutaka Itokazu, Jing Wang, Robert K Yu
The central nervous system is generated from progenitor cells that are recognized as neural stem cells (NSCs). NSCs are defined as undifferentiated neural cells that are characterized by the capacity for self-renewal and multipotency. Throughout neural development, NSCs undergo proliferation, migration, and cellular differentiation, and dynamic changes are observed in the composition of carbohydrate-rich molecules, including gangliosides. Gangliosides are sialic acid-containing glycosphingolipids with essential and multifaceted functions in brain development and NSC maintenance, which reflects the complexity of brain development...
2018: Progress in Molecular Biology and Translational Science
Duncan Hieu M Dam, Amy S Paller
An organized series of complicated biological and molecular phenomena is required for normal skin wound healing. These processes depend on normal cellular responses to cytokines, growth factors, and other mediators, such as clotting factors, prostaglandins, free radicals, and nitric oxide. In diabetic ulcers, impaired responses to these molecules lead to abnormalities in vascularization, innervation, matrix reconstruction, and reepithelialization of wounds. keratinocyte migration and proliferation on an extracellular matrix is critical in reepithelialization, but the response to growth factors is blunted in diabetes, including the insulin/IGF-1signaling axis...
2018: Progress in Molecular Biology and Translational Science
Sophie Groux-Degroote, Macarena Rodríguez-Walker, Justine H Dewald, Jose L Daniotti, Philippe Delannoy
At the outer leaflet of the plasma membrane, gangliosides are found with other glycosphingolipids, phospholipids, and cholesterol in glycolipid-enriched microdomains, in which they interact with signaling molecules including receptor tyrosine kinases and signal transducers. The role of gangliosides in the regulation of signal transduction has been reported for many cases and in different cell types. The biosynthesis of gangliosides involves specific enzymes, mainly glycosyltransferases that control together with glycohydrolases, the steady state of gangliosides at the cell surface...
2018: Progress in Molecular Biology and Translational Science
Jin-Ichi Inokuchi, Kei-Ichiro Inamori, Kazuya Kabayama, Masakazu Nagafuku, Satoshi Uemura, Shinji Go, Akemi Suzuki, Isao Ohno, Hirotaka Kanoh, Fumi Shishido
Since the successful molecular cloning in 1998 of GM3 synthase (GM3S, ST3GAL5), the enzyme responsible for initiating biosynthesis of all complex gangliosides, the efforts of our research group have been focused on clarifying the physiological and pathological implications of gangliosides, particularly GM3. We have identified isoforms of GM3S proteins having distinctive lengths of N-terminal cytoplasmic tails, and found that these cytoplasmic tails define subcellular localization, stability, and in vivo activity of GM3S isoforms...
2018: Progress in Molecular Biology and Translational Science
Taeko Miyagi, Kohta Takahashi, Koji Yamamoto, Kazuhiro Shiozaki, Kazunori Yamaguchi
Sialidases are glycosidases responsible for the removal of α-glycosidically linked sialic acid residues from carbohydrate portions of glycoproteins and glycolipids, this process being the initial step in the degradation of such glycoconjugates. Sialic acids are considered to play important roles in various biological processes largely in two ways, one related to their hydrophilic and acidic properties exerting physicochemical effects on the glycoconjugates to which they are attached, and the other as recognition sites or in an opposing fashion as masking sites...
2018: Progress in Molecular Biology and Translational Science
Roger Sandhoff, Heike Schulze, Konrad Sandhoff
Gangliosides (GGs) are cell type-specific sialic acid-containing glycosphingolipids (GSLs), which are enriched in mammalian brain. Defects in GSL metabolism cause fatal human diseases. GSLs are composed of a hydrophilic oligosaccharide linked in 1-O-position to a hydrophobic ceramide anchor, which itself is composed of a long-chain amino alcohol, the sphingoid base, and an amide-bound acyl chain. Biosynthesis of mammalian GGs and other GSLs starts with the formation of their hydrophobic ceramide anchor in the endoplasmic reticulum, followed by sequential glycosylation reactions along the secretory pathway, mainly at the luminal surface of Golgi and trans-Golgi network (TGN) membranes...
2018: Progress in Molecular Biology and Translational Science
Andre Catic
Metabolic changes are hallmarks of aging and genetic and pharmacologic alterations of relevant pathways can extend life span. In this review, we will outline how cellular biochemistry and energy homeostasis change during aging. We will highlight protein quality control, mitochondria, epigenetics, nutrient-sensing pathways, as well as the interplay between these systems with respect to their impact on cellular health.
2018: Progress in Molecular Biology and Translational Science
Michal M Masternak, Justin Darcy, Berta Victoria, Andrzej Bartke
Dwarf mice have been studied for many decades, however, the focus of these studies shifted in 1996 when it was shown by Brown-Borg and her coworkers that Ames dwarf (Prop1df ) mice are exceptionally long-lived. Since then, Snell dwarf (Pit1dw ) and growth hormone receptor knockout (GHR-KO, a.k.a. Laron dwarf) mice were also shown to be exceptionally long-lived, presumably due to their growth hormone (GH)-deficiency or -resistance, respectively. What is of equal importance in these dwarf mice is their extended health span, that is, these animals have a longer period of life lived free of frailty and age-related diseases...
2018: Progress in Molecular Biology and Translational Science
Marc T Hamilton, Deborah G Hamilton, Theodore W Zderic
There is more need for "a movement-movement" than ever before. The percentage of seniors in our population is rising exponentially. Sedentary lifestyles throughout the lifespan have become the norm, including inactive youth and a sedentary workforce. Preventable chronic diseases caused by sedentary living have both lowered the quality of life for those directly affected or their families, and have created an unsustainable economic dilemma. In this article, we explain that whether it is a sedentary student, worker, or retiree, the most neglected but essential facts are as follows...
2018: Progress in Molecular Biology and Translational Science
Pamela Anne Quiroz
The rising costs of health care in the United States continue to stimulate interest in alternative health care options among Americans. Western medicine is also beginning to pay more attention to these alternative practices and their utility for successful treatment of illness. Alternative health care practices have always been used by Hispanics whose mortality and morbidity profiles have stimulated interest from researchers. Though Hispanics occupy some of the lowest socioeconomic positions in the United States, they have higher life expectancy rates and comparable rates of morbidity for many health conditions relative to other racial/ethnic groups...
2018: Progress in Molecular Biology and Translational Science
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