An In-Depth Review For Gangliosides GM1 as regulators of neuronal survival and axon regeneration

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Phcoker

www.phcoker.com

An In-Depth Review For Gangliosides GM1 as regulators of neuronal survival and axon regeneration It has long been observed that exogenous addition of gangliosides to nerve cells in culture results in neurite sprouting and outgrowth, and enhances survival in the face of specific toxic insults. The mechanisms of these well-established observations have been elusive and range from specific interactions with growth factor receptors such as TrkA, to modification of calcium flux, to generalized and structurally nonspecific effects on the membrane milieu. Regardless of the mechanism(s), the results were sufficiently consistent to warrant human trials of injectable GM1 in a variety of human diseases including spinal cord injury, Parkinson's disease, and stroke. The results have been variable, with effects on recovery from spinal cord injury and stroke limited, and those in Parkinson's disease more encouraging. Animal models of ganglioside GM1 deficiency display some Parkinson-like symptoms that are alleviated by administration of L-DOPA or cell-permeable ganglioside mimetics, and gangliosides may be reduced in Parkinson's disease patients. Rare reports of sporadic treatment-related anti-ganglioside immune responses resulting in Guillain-BarrĂŠ syndrome have raised concerns . With ganglioside delivery involving intravenous and/or intramuscular delivery, the pharmacokinetics and pharmacodynamics of gangliosides as drugs, and their potential to enhance outcomes in human disease, are a matter for further investigation. MAG inhibition of axon regeneration (see above) is also mediated, at least in part, by complex gangliosides. MAG has several receptors on axons that act cooperatively or independently to generate intracellular signals that halt axon outgrowth . When studied in vitro, MAG inhibition of axon outgrowth from some nerve cell types (but not others) was reversed by cleaving the terminal sialic acids from gangliosides with 1

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