Ganglioside derivative LIGA20 reduces NMDA neurotoxicity in neonatal rat brain

Lipartiti, Maria; Lazzaro, A.; Manev, Hari

doi:10.1097/00001756-199210000-00025

Cited by 14 publications

(9 citation statements)

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“…Here, using the neonatal mouse model described above, we studied the effects of GM1 and LIGA20 on ethanol-induced apoptotic neurodegeneration. LIGA20 was used because it showed more potent neuroprotective effects than natural gangliosides in previous studies (Lipartiti et al, 1992;Saito et al, 1999;Wu et al, 2005). Our results indicate that GM1 and LIGA20 significantly attenuate ethanol-induced apoptotic neurodegeneration in the developing mouse brain.…”

supporting

confidence: 53%

Effects of Gangliosides on Ethanol‐Induced Neurodegeneration in the Developing Mouse Brain

Saito

Mao

Wang

et al. 2007

Alcoholism Clin & Exp Res

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supporting

confidence: 53%

Effects of Gangliosides on Ethanol‐Induced Neurodegeneration in the Developing Mouse Brain

Saito

Mao

Wang

et al. 2007

Alcoholism Clin & Exp Res

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“…Although they differ only at the fatty acid tail , the LIGA20 neuroprotective effect against gp120 is stronger than that of GM1. Our findings are consistent with previous data demonstrating that LIGA20 is pharmacologically more active than other natural gangliosides as a neuroprotective agent Lipartiti et al, 1992;Costa et al, 1994;Kharlamov et al, 1994;Saito et al, 1998). The greater potency of LIGA20 may be attributable to its chemical structure and superior membrane permeability (Wu et al, 2004).…”

Section: Discussionsupporting

confidence: 92%

“…It remains to be established whether LIGA20 activates the BDNF/ TrkB autocrine loop in vivo. LIGA20 is also neuroprotective against glutamate Lipartiti et al, 1992;Costa et al, 1993;Bachis et al, 2002). HIV-associated neuronal loss is also thought to result from glutamate released from nonneuronal cells (Dreyer and Lipton, 1995;Bezzi et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

Semisynthetic sphingoglycolipid LIGA20 is neuroprotective against human immunodeficiency virus‐gp120‐mediated apoptosis

Bachis

Mocchetti

2006

J of Neuroscience Research

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Apoptosis and neuronal atrophy are commonly seen in patients infected with the human immunodeficiency virus type 1 (HIV-1) in the late phase of infection. The HIV-1 envelope glycoprotein gp120 has been suggested to be a causal agent of neuronal loss. Therefore, blocking gp120 neurotoxicity may be an effective way to reduce the neuronal degeneration seen in HIV patients. Brain-derived neurotrophic factor (BDNF) prevents gp120-mediated apoptosis in cerebellar granule cells. However, BDNF poorly crosses the blood-brain barrier and therefore may not be a suitable therapy for HIV patients. LIGA20 is a semisynthetic sphingoglycolipid that may be a valid alternative to BDNF. In fact, it has been shown that LIGA20 mimics the neuroprotective properties of BDNF. The present study was undertaken to characterize the relative potency of LIGA20 to antagonize gp120-mediated apoptosis. Cerebellar granule cells were exposed to gp120IIIB (5 nM) or stromal-cell derived factor-1 (SDF), the natural ligand for the CXCR4 receptor to which gp120 binds, alone or in combination with LIGA20 (5 microM), and cell death/survival was determined 12 and 24 hr later by various markers of apoptosis. LIGA20 blocked the neurotoxic effect of gp120 and SDF. The neurotrophic effect of LIGA20 was reversed by K252a, a tyrosine kinase inhibitor used to block TrkB signaling, suggesting the involvement of TrkB activation. These findings provide the rationale for exploring the ability of compounds that mimic BDNF activity to reduce neuronal cell death in HIV-1-positive patients.

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“…These compounds possess very rapid onset of action. In the case of LIGA20,it is more potent than GM1 [52,70,71], can be administered by mouth [71][72][73] and has fewer side effects [74,75].…”

Section: Apoptosis Ischemic Stroke and Spinal Cord Injurymentioning

confidence: 99%

Exogenous gangliosides, neuronal plasticity and repair, and the neurotrophins

Mocchetti

2005

Cell. Mol. Life Sci.

150

117

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Gangliosides, a heterogeneous family of glycosphingolipids abundant in the brain, have been shown to affect neuronal plasticity during development, adulthood and aging. This review will examine old and recent evidence that exogenous gangliosides and in particular GM1, the prototype member of this family, exhibit multimodal neurotrophic effects. Since these compounds are a potential therapeutic tool for the treatment of various forms of acute or chronic neurodegenerative diseases, understanding the dynamic interplay of gangliosides and neuronal cells is essential in the effort to cure neurological disorders. Focus will be given to the novel and provocative hypothesis that gangliosides' neuroprotective properties may derive from their ability to mimic endogenous neurotrophic factors.

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Ganglioside derivative LIGA20 reduces NMDA neurotoxicity in neonatal rat brain

Cited by 14 publications

References 0 publications

Effects of Gangliosides on Ethanol‐Induced Neurodegeneration in the Developing Mouse Brain

Effects of Gangliosides on Ethanol‐Induced Neurodegeneration in the Developing Mouse Brain

Semisynthetic sphingoglycolipid LIGA20 is neuroprotective against human immunodeficiency virus‐gp120‐mediated apoptosis

Exogenous gangliosides, neuronal plasticity and repair, and the neurotrophins

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