Alteration of the sialylation pattern and memory deficits by injection of Aβ(25–35) into the hippocampus of rats

Limón, Ilhuicamina Daniel; Ramírez, Eleazar; Díaz, Alfonso; Mendieta, Liliana; Mayoral, Miguel Ángel; Espinosa, Blanca; Guevara, Jorge; Zenteno, Edgar

doi:10.1016/j.neulet.2011.03.006

Cited by 23 publications

(8 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This disialylated structure has been associated with various forms of cancer, 46 and the increase in α2-6-linked sialic acid-containing structures like this one has also been correlated to an enhanced degenerative state in the brain. 47 Similar outcomes were observed in other neurodegenerative diseases such as Alzheimer’s disease (AD), where sialylation events occurring in the serum N -glycome matched that in PD. However, the total O -glycome of AD seems yet to be elucidated also.…”

Section: Discussionsupporting

confidence: 57%

The O-Glycome of Human Nigrostriatal Tissue and Its Alteration in Parkinson’s Disease

et al. 2021

View full text Add to dashboard Cite

O -Glycosylation changes in misfolded proteins are of particular interest in understanding neurodegenerative conditions such as Parkinson’s disease (PD) and incidental Lewy body disease (ILBD). This work outlines optimizations of a microwave-assisted nonreductive release to limit glycan degradation and employs this methodology to analyze O -glycosylation on the human striatum and substantia nigra tissue in PD, ILBD, and healthy controls, working alongside well-established reductive release approaches. A total of 70 O -glycans were identified, with ILBD presenting significantly decreased levels of mannose-core ( p = 0.017) and glucuronylated structures ( p = 0.039) in the striatum and PD presenting an increase in sialylation ( p < 0.001) and a decrease in sulfation ( p = 0.001). Significant increases in sialylation ( p = 0.038) in PD were also observed in the substantia nigra. This is the first study to profile the whole nigrostriatal O -glycome in healthy, PD, and ILBD tissues, outlining disease biomarkers alongside benefits of employing orthogonal techniques for O -glycan analysis.

show abstract

Section: Discussionsupporting

confidence: 57%

The O-Glycome of Human Nigrostriatal Tissue and Its Alteration in Parkinson’s Disease

et al. 2021

View full text Add to dashboard Cite

show abstract

“…The hippocampal regions with increased PSA expression were also the regions where Aβ plaques, neurofibrillary tangles and neuronal loss occur and where neurons undergo remodeling (Jin et al, 2004). Consistent with this finding, acute injection of Aβ into rat hippocampus caused an increased PSA expression (Limón et al, 2011), which suggested an important role of PSA in neurogenesis-associated AD pathogenesis.…”

Section: Psa-ncam In Adult Neurogenesissupporting

confidence: 66%

Sialometabolism in Brain Health and Alzheimer’s Disease

Rawal

Zhao

2021

Front. Neurosci.

View full text Add to dashboard Cite

Sialic acids refer to a unique family of acidic sugars with a 9-carbon backbone that are mostly found as terminal residues in glycan structures of glycoconjugates including both glycoproteins and glycolipids. The highest levels of sialic acids are expressed in the brain where they regulate neuronal sprouting and plasticity, axon myelination and myelin stability, as well as remodeling of mature neuronal connections. Moreover, sialic acids are the sole ligands for microglial Siglecs (sialic acid-binding immunoglobulin-type lectins), and sialic acid-Siglec interactions have been indicated to play a critical role in the regulation of microglial homeostasis in a healthy brain. The recent discovery of CD33, a microglial Siglec, as a novel genetic risk factor for late-onset Alzheimer’s disease (AD), highlights the potential role of sialic acids in the development of microglial dysfunction and neuroinflammation in AD. Apart from microglia, sialic acids have been found to be involved in several other major changes associated with AD. Elevated levels of serum sialic acids have been reported in AD patients. Alterations in ganglioside (major sialic acid carrier) metabolism have been demonstrated as an aggravating factor in the formation of amyloid pathology in AD. Polysialic acids are linear homopolymers of sialic acids and have been implicated to be an important regulator of neurogenesis that contributes to neuronal repair and recovery from neurodegeneration such as in AD. In summary, this article reviews current understanding of neural functions of sialic acids and alterations of sialometabolism in aging and AD brains. Furthermore, we discuss the possibility of looking at sialic acids as a promising novel therapeutic target for AD intervention.

show abstract

“…In addition, RA-SH-SY5Y cells display significant variability of Sia expression, probably due to the different levels of the differentiation process that is induced in them. Indeed, Sias linked to gangliosides are essential for cell interactions with the microenvironment and seem to be involved in fundamental neurobiological processes performed by these glycolipids, such as axonal and dendritic growth, synapse formation and synaptic transmission [ 48 , 65 , 66 , 67 , 68 , 69 , 70 ]. Among RA-SH-SY5Y cells, which show neuronal-like plasticity, higher levels of Sias may therefore be expressed at more advanced differentiation stages.…”

Section: Discussionmentioning

confidence: 99%

“…Several investigations on Sia expression in post-mortem human brains affected by neurodegenerative diseases, such as AD and PD, or administration of Aβ peptides into the hippocampus of rats reported sialylation dysregulation, particularly in cerebral regions exhibiting tissue plasticity most frequently affected by these pathologies [ 40 , 41 , 46 , 48 , 49 , 50 , 51 , 52 ].…”

Section: Introductionmentioning

confidence: 99%

Correlation between Sialylation Status and Cell Susceptibility to Amyloid Toxicity

Sgambati

Tani

Leri

et al. 2022

Cells

View full text Add to dashboard Cite

The interaction between the cell membrane and misfolded protein species plays a crucial role in the development of neurodegeneration. This study was designed to clarify the relationship between plasma membrane composition in terms of the differently linked sialic acid (Sia) content and cell susceptibility to toxic and misfolded Aβ-42 peptides. The sialylation status in different cell lines was investigated by lectin histochemistry and confocal immunofluorescence and then correlated with the different propensities to bind amyloid fibrils and with the relative cell susceptibility to amyloid damage. This study reveals that expressions of Sias α2,3 and α2,6 linked to galactose/N-acetyl-galactosamine, and PolySia are positively correlated with Aβ-42-induced cell toxicity. PolySia shows an early strong interaction with amyloid fibrils, favoring their binding to GM1 ganglioside containing α2,3 galactose-linked Sia and a loss of cell viability. Our findings demonstrate that cell lines with a prevailing plastic neuron-like phenotype and high monoSia and PolySia contents are highly susceptible to amyloid Aβ-42 toxicity. This toxicity may involve a change in neuron metabolism and promote a compensative/protective increase in PolySia, which, in turn, could favor amyloid binding to GM1, thus exacerbating cell dysmetabolism and further amyloid aggregation.

show abstract

Alteration of the sialylation pattern and memory deficits by injection of Aβ(25–35) into the hippocampus of rats

Cited by 23 publications

References 15 publications

The O-Glycome of Human Nigrostriatal Tissue and Its Alteration in Parkinson’s Disease

The O-Glycome of Human Nigrostriatal Tissue and Its Alteration in Parkinson’s Disease

Sialometabolism in Brain Health and Alzheimer’s Disease

Correlation between Sialylation Status and Cell Susceptibility to Amyloid Toxicity

Contact Info

Product

Resources

About