Sex-Related Abnormalities in Substantia Nigra Lipids in Parkinson’s Disease

Seyfried, Thomas N.; Choi, Hyo-S.; Chevalier, Amber C.; Hogan, D E; Akgoc, Zeynep; Schneider, Jay S.

doi:10.1177/1759091418781889

Cited by 83 publications

(104 citation statements)

References 58 publications

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“…The ganglioside mean content in the brain from seven Parkinson's disease male with age ranging from 67 to 95 was found to be reduced by 22% compared to the brain content of 12 healthy controls with the same age. No difference was found between control and Parkinson's disease females [30].…”

Section: Gm1 Of Neuronal Plasma Membrane In the Central Nervous Systementioning

confidence: 69%

GM1 Ganglioside Is A Key Factor in Maintaining the Mammalian Neuronal Functions Avoiding Neurodegeneration

Chiricozzi

Lunghi

Biase

et al. 2020

IJMS

140

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Many species of ganglioside GM1, differing for the sialic acid and ceramide content, have been characterized and their physico-chemical properties have been studied in detail since 1963. Scientists were immediately attracted to the GM1 molecule and have carried on an ever-increasing number of studies to understand its binding properties and its neurotrophic and neuroprotective role. GM1 displays a well balanced amphiphilic behavior that allows to establish strong both hydrophobic and hydrophilic interactions. The peculiar structure of GM1 reduces the fluidity of the plasma membrane which implies a retention and enrichment of the ganglioside in specific membrane domains called lipid rafts. The dynamism of the GM1 oligosaccharide head allows it to assume different conformations and, in this way, to interact through hydrogen or ionic bonds with a wide range of membrane receptors as well as with extracellular ligands. After more than 60 years of studies, it is a milestone that GM1 is one of the main actors in determining the neuronal functions that allows humans to have an intellectual life. The progressive reduction of its biosynthesis along the lifespan is being considered as one of the causes underlying neuronal loss in aged people and severe neuronal decline in neurodegenerative diseases. In this review, we report on the main knowledge on ganglioside GM1, with an emphasis on the recent discoveries about its bioactive component.

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Section: Gm1 Of Neuronal Plasma Membrane In the Central Nervous Systementioning

confidence: 69%

GM1 Ganglioside Is A Key Factor in Maintaining the Mammalian Neuronal Functions Avoiding Neurodegeneration

Chiricozzi

Lunghi

Biase

et al. 2020

IJMS

140

View full text Add to dashboard Cite

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“…Interestingly, neuronal loss in male SNc is accompanied by a significant reduction in total ganglioside content, especially neuronal-or synaptic-enriched gangliosides GD1a and GT1b. No significant abnormalities were found in female PD subjects [93]. Accordingly, it has been demonstrated that estradiol acts as homeostatic modulator of lipid rafts, thus preserving lipid balance in neuronal membrane microdomains [94].…”

Section: Dopaminergic Neurodegenerationmentioning

confidence: 91%

Parkinson’s Disease in Women and Men: What’s the Difference?

Cerri¹,

Mus²,

Blandini³

2019

JPD

445

309

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Increasing evidence points to biological sex as an important factor in the development and phenotypical expression of Parkinson's disease (PD). Risk of developing PD is twice as high in men than women, but women have a higher mortality rate and faster progression of the disease. Moreover, motor and nonmotor symptoms, response to treatments and disease risk factors differ between women and men. Altogether, sex-related differences in PD support the idea that disease development might involve distinct pathogenic mechanisms (or the same mechanism but in a different way) in male and female patients. This review summarizes the most recent knowledge concerning differences between women and men in PD clinical features, risk factors, response to treatments and mechanisms underlying the disease pathophysiology. Unraveling how the pathology differently affect the two sexes might allow the development of tailored interventions and the design of innovative programs that meet the distinct needs of men and women, improving patient care.

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“…Reduced expression of GM1, GD1a, and GD1b were reported in the occipital cortex of PD patients using HPTLC [ 19 ]. Using HPTLC, we have also recently described significant decreases in GD1a, GD1b, and GT1b in SN from male PD patients, along with a smaller magnitude decrease in GM1 that did not reach statistical significance [ 20 ]. In contrast, we found no significant changes in levels of GM3, GM2, or GD3 in PD SN.…”

Section: Introductionmentioning

confidence: 99%

Altered expression of genes involved in ganglioside biosynthesis in substantia nigra neurons in Parkinson’s disease

Schneider

2018

PLoS ONE

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Reduced expression of GM1 and other major brain gangliosides GD1a, GD1b and GT1b have been reported in Parkinson’s disease (PD) brain. Mechanisms underlying these changes are unclear but may be due to a deficit in the ganglioside biosynthetic process. The present study examined the extent to which deficits in gene expression of key biosynthetic enzymes involved in synthesis of GM1 and GD1b (B3galt4) and GD1a and GT1b (St3gal2) exist in neuromelanin-containing neurons in the PD substantia nigra (SN). In situ hybridization histochemistry was used to examine gene expression of B3GALT4 and ST3GAL2 in neuromelanin-containing neurons in the SN in 8 normal controls (61–92 yrs.) and 7 PD subjects (77–95 yrs). There was a significant decrease in both B3GALT4 and ST3GAL2 gene expression in residual neuromelanin-containing cells in the SN of PD patients compared to age-matched neurologically normal controls. These changes appeared to be cell-type specific as abundant B3GALT4 and ST3GAL2 gene expression was observed in non-neuromelanin containing neurons located outside of the SN in the PD brain. These data show that residual neuromelanin-containing neurons in the PD SN have decreased expression of the ganglioside biosynthetic genes B3GALT4 and ST3GAL2, consistent with previous reports of decreased levels of gangliosides GM1, GD1a, GD1b and GT1b in the PD SN. These changes may increase the vulnerability of these neurons to degeneration in response to a variety of potential stressors.

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Sex-Related Abnormalities in Substantia Nigra Lipids in Parkinson’s Disease

Cited by 83 publications

References 58 publications

GM1 Ganglioside Is A Key Factor in Maintaining the Mammalian Neuronal Functions Avoiding Neurodegeneration

GM1 Ganglioside Is A Key Factor in Maintaining the Mammalian Neuronal Functions Avoiding Neurodegeneration

Parkinson’s Disease in Women and Men: What’s the Difference?

Altered expression of genes involved in ganglioside biosynthesis in substantia nigra neurons in Parkinson’s disease

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