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Abstract
Following our initial reports on subnormal levels of GM1 in the substantia nigra and occipital cortex of Parkinson’s disease (PD) patients, we have examined additional tissues from such patients and found these are also deficient in the ganglioside. These include innervated tissues intimately involved in PD pathology such as colon, heart and others, somewhat less intimately involved, such as skin and fibroblasts. Finally, we have analyzed GM1 in peripheral blood mononuclear cells, a type of tissue apparently with no direct innervation, and found those too to be deficient in GM1. Those patients were all afflicted with the sporadic form of PD (sPD), and we therefore conclude that systemic deficiency of GM1 is a characteristic of this major type of PD. Age is one factor in GM1 decline but is not sufficient; additional GM1 suppressive factors are involved in producing sPD. We discuss these and why GM1 replacement offers promise as a disease-altering therapy.
Highlights
Parkinson’s disease (PD) was earlier viewed primarily as a movement disorder involving the nigral dopaminergic (DA) neurons of the substantia nigra pars compacta (SNpc) but has gradually come to be recognized as a multi-system disease involving virtually all neurons of the central nervous system (CNS) and peripheral nervous system (PNS)
The discovery that aSyn aggregates can propagate from cell-to-cell in a prion-like manner [7] led to the question of disease origin and the proposal that PD comprises two subtypes, a brain-first form with aSyn aggregates migrating from the brain to peripheral sites, and a body-first type with initial pathology in the enteric or peripheral autonomic nervous system with migration in the opposite direction [8]
In a more detailed study of Peripheral blood mononuclear cells (PBMCs), we recently found such GM1 deficiency to be more pronounced in PD patients with the glucocerebrosidase (GBA) malfunction than in those with the more common form of sporadic form of PD (sPD) [17], similar to the result in Supplementary
Summary
Parkinson’s disease (PD) was earlier viewed primarily as a movement disorder involving the nigral dopaminergic (DA) neurons of the substantia nigra pars compacta (SNpc) but has gradually come to be recognized as a multi-system disease involving virtually all neurons of the central nervous system (CNS) and peripheral nervous system (PNS). We have been interested in the role of GM1 ganglioside, considering its subnormal expression found in the brain and have considered this in relation to the diverse pathophysiological manifestations of this complex disorder. Pathophysiological disabling of neurons outside the CNS was well revealed in the ground-breaking studies of Braak and coworkers using Lewy pathologies as the chief neuropathological indicator [3,4,5] and by the work of others [6]. Such findings were effectively correlated with various nonmotor symptoms of PD.
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