Regulation of axonal development by plasma membrane gangliosides

Abad‐Rodríguez, José; Robotti, Andrea

doi:10.1111/j.1471-4159.2007.04713.x

Cited by 39 publications

(32 citation statements)

References 86 publications

(142 reference statements)

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“…GD1a serves as a reserve for the spatially regulated generation of GM1 by the sialidase Neu3 in various neural compartments (Tettamanti et al, 1972;Da Silva et al, 2005). Since both GT1b and GD1a are ligands for the myelin-associated glycoprotein and play a role in myelin-axon adhesion and axon stability (Abad-Rodriguez and Robotti, 2007), their deficit in HD is also likely to affect brain functions.…”

Section: Discussionmentioning

confidence: 99%

Impaired Ganglioside Metabolism in Huntington's Disease and Neuroprotective Role of GM1

Maglione¹,

Marchi²,

Pardo³

et al. 2010

J. Neurosci.

124

152

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Huntington's disease (HD) is a neurodegenerative disorder caused by the expansion of a polyglutamine stretch in the protein huntingtin (Htt). HD neurons are dysfunctional at multiple levels and have increased susceptibility to stress and apoptotic stimuli. We have discovered that synthesis of the ganglioside GM1 is reduced in fibroblasts from HD patients and in cell and animal models of HD, and that decreased GM1 levels contribute to heighten HD cell susceptibility to apoptosis. The apoptotic susceptibility is recapitulated through inhibition of ganglioside synthesis in wild-type striatal cells, suggesting that decreased GM1 levels might be one of the key events leading to HD pathogenesis and progression. Administration of GM1 restores ganglioside levels in HD cells and promotes activation of AKT and phosphorylation of mutant Htt, leading to decreased mutant Htt toxicity and increased survival of HD cells. Our data identify GM1 as a potential treatment for HD.

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Section: Discussionmentioning

confidence: 99%

Impaired Ganglioside Metabolism in Huntington's Disease and Neuroprotective Role of GM1

Maglione¹,

Marchi²,

Pardo³

et al. 2010

J. Neurosci.

124

152

View full text Add to dashboard Cite

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“…While future experiments will be necessary to determine the underlying mechanisms of altered synaptic functions including potential compensatory mechanisms, various misregulated signaling pathways could be involved. To give just one example, altered oxidative stress and reactive oxygen species levels (ROS) are a key convergent feature of parkinsonism caused by various factors, including parkin mutations (Greenamyre and Hastings 2004; Rodriguez-Navarro et al 2007). At the same time, ROS signaling is also necessary for normal hippocampal LTP (Almaguer-Melian et al 2000; Watson et al 2006), suggesting a possible role in the altered synaptic physiology.…”

Section: Discussionmentioning

confidence: 99%

Altered Hippocampal Synaptic Physiology in Aged Parkin-Deficient Mice

2010

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We examined synaptic function in the hippocampus of aged mice deficient for the Parkinson’s disease-linked protein, parkin. Surprisingly, heterozygous but not homozygous parkin-deficient mice exhibited impairments in basal excitatory synaptic strength. Similarly heterozygous mice exhibited broad deficits in paired-pulse facilitation, while homozygous parkin-deficient mice exhibited more restricted deficits. In contrast to the measurements of basal synaptic function, synaptic plasticity was not altered in aged heterozygous parkin-deficient mice, but was enhanced in aged homozygous parkin-deficient mice, due to an absence of age-related decline. These findings of differential synaptic phenotypes in heterozygous vs. homozygous parkin deficiency suggest compensatory responses to genetic abnormalities could play an important role during the development of pathology in response to parkin deficiency.

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“…N-acetylneuraminic (Neu5Ac) and gangliosides containing this form of SA play a key role in neuronal development during the first stages of life (Abad-Rodríguez & Robotti, 2007), taking part in pathogen adhesion mechanisms, acting as false receptors avoiding intestinal cellepathogen binding (Newburg, Ruiz-Palacios, & Morrow, 2005;Usuki et al, 2006), and participating in the activation and proliferation of T cells and Th1 and Th2 lymphocytes (Ebel, Schmitt, Peter-Katalinic, Kniep, & Muhlradt, 1992). The SA form Neu5Gc cannot be incorporated to glycoconjugates (including gangliosides) or synthesized de novo.…”

Section: Introductionmentioning

confidence: 99%