China
Africa
Explore chapters and articles related to this topic
The Scientific Basis of Medicine
Published in John S. Axford, Chris A. O'Callaghan, Medicine for Finals and Beyond, 2023
Chris O'Callaghan, Rachel Allen
Endocytosed proteins and other materials are degraded within membrane-bound lysosomes, which store the hydrolytic enzymes required for such degradation. Deficiency of a lysosomal enzyme causes the neurological condition Tay–Sachs disease in which gangliosides accumulate in the brain causing neural degeneration and early death.
Carrier Screening For Inherited Genetic Conditions
Published in Vincenzo Berghella, Obstetric Evidence Based Guidelines, 2022
Whitney Bender, Lorraine Dugoff
Clinical features: This is the most well-known disorder affecting the Ashkenazi Jewish population. In this lysosomal storage disease, GM2 gangliosides accumulate throughout the body due to functional deficiency in hexosaminidase A. The accumulation of these gangliosides in the central nervous system results in progressive functional decline. An apparently healthy child begins to lose skills around 4–6 months of age, and there is a progressive neurologic decline leading to blindness, seizures, and unresponsiveness. Death usually occurs by the age of 4–6.
Neuroprotection and Repair after Spinal Cord Injury
Published in Jacques Corcos, Gilles Karsenty, Thomas Kessler, David Ginsberg, Essentials of the Adult Neurogenic Bladder, 2020
Gangliosides are found in high concentration in the outer cell membranes of CNS cells, especially in the vicinity of synapses. The proposed mechanisms of action of exogenously administered gangliosides include antiexcitotoxic activities, prevention of apoptosis, augmentation of neurite outgrowth, and induction of neuronal sprouting and regeneration.58–61 The proposed neuroregenerative benefits of GM-1 ganglioside provided the impetus for clinical trials in humans with acute SCI, but results had no statistically significant improvement with treatment.62,63
Sandhoff disease in the elderly: a case study
Published in Amyotrophic Lateral Sclerosis and Frontotemporal Degeneration, 2022
Leidy García Morales, Reinaldo Gaspar Mustelier Bécquer, Laura Pérez Joglar, Tatiana Zaldívar Vaillant
Sandhoff disease is an infrequent genetically-caused disorder with a recessive inheritance pattern. It belongs to the gangliosidosis GM2 group and it is produced by mutations in gen HEXB (chromosome 5q13) leading to reduced activity of enzymes β-hexosaminidase A and B, and deposition of sphingolipids (ganglioside GM2 and globoside) in brain and other organs. Nearly, 40 specific mutations causing this disease have been reported (1). Clinical manifestations and age of onset depend on the enzymatic residual catabolic activity, associated with infantile, juvenile, and adult variants (2). The homozygous state is associated with earlier onset and greater disease severity (1). The clinical manifestations of the adult variant are heterogeneous and poorly characterized. It may appear as a combination of motor neuron disease, spinocerebellar ataxia, neuropathy, autonomic dysfunction, cognitive impairment, movement disorders, and psychiatric manifestations (2–4). At this time, there is no effective treatment for this disease (2).
Immune checkpoint inhibitors: a new landscape for extensive stage small cell lung cancer treatment
Published in Expert Review of Respiratory Medicine, 2021
Andrea Bianco, Vito D’Agnano, Maria Gabriella Matera, Luigi Della Gravara, Fabio Perrotta, Danilo Rocco
Gangliosides are a group of cell surface glycosphingolipids participating in cell-cell recognition, adhesion and signal transduction. BMS-986,012 is a first-in-class, fully human monoclonal Ab that binds to fucosyl-GM1, a normally expressed ganglioside in a subset of peripheral sensory neurons and dorsal root ganglia, that has been shown to be highly expressed on SCLC cells. Consequently, antibody-dependent cell-mediated cytotoxicity will be enhanced. When combined with nivolumab, BMS-986,012 showed promising antitumor activity in SCLC patients, who relapsed after or were refractory to first-line therapy, with partial response achieved in 4 (2 unconfirmed) of the 16 patients evaluable for efficacy. Additionally, treatment has been well tolerated. Only two patients experienced G3/4 TRAEs, while the most common adverse event associated to immunotherapy has been generalized pruritus (71%). Further data on efficacy are still pending [102].
Immunomodulatory regulation by heat-labile enterotoxins and potential therapeutic applications
Published in Expert Review of Vaccines, 2021
Mary-Peyton A. Knapp, Taylor A. Johnson, Madison K. Ritter, Robert O. Rainer, Steven E. Fiester, Jennifer T. Grier, Terry D. Connell, Sergio Arce
The mechanisms by which gangliosides affect cellular function are extremely varied and new contributions are still being discovered. Gangliosides are believed to effect change through their glycans, composed of one or more sialic acid residues, that are attached to ceramide lipids, which anchor the molecules into plasma membranes [17,21]. These glycans are involved in recognition of soluble molecules from the extracellular environment and on the surface of other cells and can contribute to the modulation of protein interactions on the same cellular membrane [17,21]. Through glycan-mediated modulation of signal transduction pathways and cytokine release, gangliosides are able to play a role in the number, morphology and function of immune cells [20,21,27,35]. Gangliosides also have been shown to regulate the responsiveness of cells to proteins such as insulin, epidermal growth factor, and vascular endothelial growth factor receptors via lateral interactions in the same membranes in which these molecules reside [17]. In addition, modulation of these responses contributes to alterations in angiogenesis, metastasis and cell movement, as well as immune suppression and immune modulation [20,21,27,35].