Gangliosides in treatment of neural injury and disease

Abstract

AbstractGangliosides are being used therapeutically to treat a variety of nervous system disorders including peripheral neuropathies and stroke. Gangliosides (over 70 molecular species) are glycosphingolipids found in highest concentration in neural tissue. They are thought to be functional in such diverse biological processes as embryogenesis and cell death, and specifically in membrane‐mediated processes (cell‐cell interactions, ionic balance, synaptic transmission, and receptor‐mediated information transfer). Their distribution changes during neural development, indicative of differential roles for each molecular species at critical stages of development. Ganglioside distribution differs during abnormal development or after neural injury due to trauma or disease. In vivo and in vitro studies have shown that exogenous gangliosides can substitute (structrally and functionally) for the endogenous molecules. This has made it possible to investigate the molecular mechanisms of ganglioside function in situ. During the genesis of these studies it became clear that exogenous gangliosides were able to protect the chemical and morphological changes associated with neural (CNS and PNS) tissue injury (mechanical, ischemic, and neurotoxic). This protective effect has been characterized by facilitated functional recovery in a number of CNS injury paradigms. The mechanism(s) for the facilitative effect of ganglioside treatment is unidentified. Data support a number of hypotheses. One contends that gangliosides can acutely reduce the extent of CNS injury and pathology by protection of membrane structure/function, thereby leading to reduced functional deficits and therefore to increased potential for functional recovery. Another hypothesis supports the view that these glycosphingolipids may promote neuronal regeneration through modulation of trophic factors. Studying the effects of exogenous gangliosides on CNS injury is leading to further insight into the critical functions of endogenous gangliosides as well as focusing attention on the potential of exogenous gangliosides as a therapeutic treatment of traumatic and degenerative CNS disorders.