Abstract
Glucocerebrosides are sphingolipid components of cell membranes that intervene in numerous cell biological processes and signaling pathways and that deregulation is implicated in human diseases such as Gaucher disease and Parkinson's disease. In the present study, we conducted a systematic review using document co-citation analysis, clustering and visualization tools to explore the trends and knowledge structure of glucocerebrosides research as indexed in the Science Citation Index Expanded database (1956—present). A co-citation network of 5,324 publications related to glucocerebrosides was constructed. The analysis of emerging categories and keywords suggested a growth of research related to neurosciences over the last decade. We identified ten major areas of research (e.g., clusters) that developed over time, from the oldest (i.e., on glucocerebrosidase protein or molecular analysis of the GBA gene) to the most recent ones (i.e., on drug resistance in cancer, pharmacological chaperones, or Parkinson's disease). We provided for each cluster the most cited publications and a description of their intellectual content. We moreover identified emerging trends in glucocerebrosides research by detecting the surges in the rate of publication citations in the most recent years. In conclusion, this study helps to apprehend the most significant lines of research on glucocerebrosides. This should strengthen the connections between scientific communities studying glycosphingolipids to facilitate advances, especially for the most recent researches on cancer drug resistance and Parkinson's disease.
Highlights
Glucocerebrosides are components of cell membranes in organisms from bacteria to humans
As biologically active components of cell membranes, glucocerebrosides and their derived glycosphingolipids intervene in several biological processes including embryogenesis (Yamashita et al, 1999), cell polarity (Zhang et al, 2011), cell adhesion and migration (Proia, 2003; Furukawa et al, 2004), and energy homeostasis (Nordstrom et al, 2013) and regulate the activity of plasma membrane proteins, including protein tyrosine kinases (Suzuki, 2012)
Taking into account the 10 most cited publications of each cluster, we propose a brief description of the intellectual content of the ten major clusters ranked by their size as follow: Cluster #0 (Parkinson’s disease): This cluster includes publications exploring the links between glucocerebrosidase, glucocerebrosides, and synucleinopathies such as Parkinson’s disease and Dementia with Lewy bodies
Summary
Glucocerebrosides ( referred to as glucosylceramides) are components of cell membranes in organisms from bacteria to humans. In 1934, the French gynecologist Henriette Aghion identified glucocerebrosides as the lipids that accumulate in the enlarged spleen and liver of patients with Gaucher disease (ORPHA355), a lysosomal storage disorder with three clinical types: nonneuropathic (type 1); acute neuropathic (type 2); and chronic neuropathic (type 3) (Aghion, 1934; Stirnemann et al, 2017). This eventually led to the discovery that Gaucher disease is due to loss-of-function mutations present on both alleles of the GBA gene encoding glucocerebrosidase. Glucocerebrosides have taken center stage in the field of neurodegeneration since the presence of GBA mutation on a single allele has been associated to increased risks for Parkinson’s disease (Sidransky et al, 2009) and dementia with Lewy bodies (Nalls et al, 2013), the two most common dementing neurodegenerative diseases after Alzheimer’s disease
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