Abstract
We have endeavored in this review to summarize our findings, which point to a systemic deficiency of ganglioside GM1 in Parkinson’s disease (PD) tissues. These include neuronal tissues well known to be involved in PD, such as substantia nigra of the brain and those of the peripheral nervous system, such as the colon and heart. Moreover, we included skin and fibroblasts in the study as well as peripheral blood mononuclear cells; these are tissues not directly involved in neuronal signaling. We show similar findings for ganglioside GD1a, which is the metabolic precursor to GM1. We discuss the likely causes of these GM1 deficiencies and the resultant biochemical mechanisms underlying loss of neuronal viability and normal functioning. Strong support for this hypothesis is provided by a mouse PD model involving partial GM1 deficiency based on mono-allelic disruption of the B4galnt1 gene. We point out that progressive loss of GM1/GD1a occurs in the periphery as well as the brain, thus obviating the need to speculate PD symptom transfer between these tissues. Finally, we discuss how these findings point to a potential disease-altering therapy for PD:GM1 replacement, as is strongly implicated in animal studies and clinical trials.
Highlights
The same may be said for ganglioside GD1a, which is identical in structure to GM1 but possesses an additional sialic acid attached to the terminal galactose of GM1 (Figure 1) [2]
We recently carried out a more detailed study of PBMC in which we found more severe GM1 deficiency in Parkinson’s disease (PD) patients with glucocerebrosidase malfunction than in PD patients with more ordinary sporadic PD [9]
We proposed GM1 deficiency in PBMC as a method for early diagnosis of those two forms of PD
Summary
The numerous glycosphingolipids that occur in the nervous system and elsewhere are clearly involved in metabolic and pathological changes that accompany Parkinson’s disease [1], but one such molecule, GM1 ganglioside, has received focused attention from several workers for its prominent role in both the etiology and potential treatment of this neurodegenerative condition. That terminal sialic acid is readily removed by NEU3 neuraminidase, which is situated close to GD1a in the neuronal membrane [3]. This review attempts to summarize our recently published evidence showing that the salient feature of GM1 in regard to PD is its subnormal level, especially in neurons but in other cell types as well. Such deficiency prevents the normal functioning of cells dependent on an adequate level of this ganglioside, resulting in their gradual quiescence and eventual death.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
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
