Abstract
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.
Highlights
Parkinson’s disease (PD) is a progressive disorder primarily characterized by degeneration of substantia nigra (SN) dopaminergic neurons with associated loss of dopamine (DA) in the striatum, and accumulation of insoluble protein aggregates, with α-synuclein being the most abundant component [1]
There were no significant differences between the ages or post-mortem intervals (PMI) between the neurologically normal control subjects and PD subjects (Table 1)
The results reported here show for the first time, decreases in gene expression of the glycosyltransferase B3GALT4 (GM1/GD1b synthase) and the sialyltransferase ST3GAL2 in neuromelanin-containing neurons in the PD SN compared to non-PD controls
Summary
Parkinson’s disease (PD) is a progressive disorder primarily characterized by degeneration of substantia nigra (SN) dopaminergic neurons with associated loss of dopamine (DA) in the striatum (caudate nucleus and putamen), and accumulation of insoluble protein aggregates (in Lewy bodies and Lewy neurites), with α-synuclein being the most abundant component [1]. Ganglioside-related gene expression in PD assigned to Thomas Jefferson University.our adherence to PLOS ONE policies on sharing data and materials. In addition to the potential disease mechanisms listed above, there has been recent interest in the role of lipids in neurodegenerative diseases and in particular, in the pathogenesis of PD. A recent plasma metabolic profiling study suggested that abnormal metabolic changes in PD plasma were mainly associated with mitochondrial function and lipid metabolism [7]. Mutations in the beta-glucosidase gene (GBA) coding for glucocerebrosidase, which breaks down glucosylceramide into glucose and ceramide, have been suggested to be an important risk factor for development of sporadic PD [8]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
