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Mitochondrial dysfunction in NPC1-deficiency is not rescued by drugs targeting the glucosylceramidase GBA2 and the cholesterol-binding proteins TSPO and StARD1
Wheeler, S.; Bhardwaj, M.; Kenyon, V.; Guimaraes Da Lomba Ferraz, M.J.; Aerts, J.M.F.G.; Sillence, D.J. 2024
Mitochondrial dysfunction in NPC1-deficiency is not rescued by drugs targeting the glucosylceramidase GBA2 and the cholesterol-binding proteins TSPO and StARD1
Article / Letter to editor
open access
Trans-cyclosulfamidate mannose-configured cyclitol allows isoform-dependent inhibition of GH47 α-d-mannosidases through a bump–hole strategy
Males, A.; Kok, K.; Nin-Hill, A.; Koster, N. de; Beukel, S. van den; Beenakker, T.J.M.; ... ; Artola Perez de Azanza, M.E. 2023
Trans-cyclosulfamidate mannose-configured cyclitol allows isoform-dependent inhibition of GH47 α-d-mannosidases through a bump–hole strategy
Article / Letter to editor
open access
The development of a broad-spectrum retaining β-exo-galactosidase activity-based probe.
Kuo, C.L.; Su, Q.; Nieuwendijk, A.M.C.H. van den; Beenakker, T.J.M.; Offen, W.A.; Willems, L.I.; ... ; Aerts, J.M.F.G. 2023
The development of a broad-spectrum retaining β-exo-galactosidase activity-based probe.
Article / Letter to editor
open access
2024-03-16T00:00:00Z
Acid β-galactosidase (GLB1) and galactocerebrosidase (GALC) are retaining exo-β-galactosidases involved in lysosomal glycoconjugate metabolism. Deficiency of GLB1 may result in the lysosomal... Show moreAcid β-galactosidase (GLB1) and galactocerebrosidase (GALC) are retaining exo-β-galactosidases involved in lysosomal glycoconjugate metabolism. Deficiency of GLB1 may result in the lysosomal storage disorders GM1 gangliosidosis, Morquio B syndrome, and galactosialidosis, and deficiency of GALC may result in Krabbe disease. Activity-based protein profiling (ABPP) is a powerful technique to assess the activity of retaining glycosidases in relation to health and disease. This work describes the use of fluorescent and biotin-carrying activity-based probes (ABPs) to assess the activity of both GLB1 and GALC in cell lysates, culture media, and tissue extracts. The reported ABPs, which complement the growing list of retaining glycosidase ABPs based on configurational isomers of cyclophellitol, should assist in fundamental and clinical research on various β-galactosidases, whose inherited deficiencies cause debilitating lysosomal storage disorders. Show less
Fluorescence polarisation activity-based protein profiling for the identification of deoxynojirimycin-type inhibitors selective for lysosomal retaining alpha- and beta-glucosidases
Gracht, D. van der; Rowland, R.J.; Roig-Zamboni, V.; Guimaraes Da Lomba Ferraz, M.J.; Louwerse, G.A.M.; Geurink, P.P.; ... ; Artola Perez de Azanza, M.E. 2023
Fluorescence polarisation activity-based protein profiling for the identification of deoxynojirimycin-type inhibitors selective for lysosomal retaining alpha- and beta-glucosidases
Article / Letter to editor
open access
Lysosomal exoglycosidases are responsible for processing endocytosed glycans from the non-reducing end to produce the corresponding monosaccharides. Genetic mutations in a particular lysosomal... Show moreLysosomal exoglycosidases are responsible for processing endocytosed glycans from the non-reducing end to produce the corresponding monosaccharides. Genetic mutations in a particular lysosomal glycosidase may result in accumulation of its particular substrate, which may cause diverse lysosomal storage disorders. The identification of effective therapeutic modalities to treat these diseases is a major yet poorly realised objective in biomedicine. One common strategy comprises the identification of effective and selective competitive inhibitors that may serve to stabilize the proper folding of the mutated enzyme, either during maturation and trafficking to, or residence in, endo-lysosomal compartments. The discovery of such inhibitors is greatly aided by effective screening assays, the development of which is the focus of the here-presented work. We developed and applied fluorescent activity-based probes reporting on either human GH30 lysosomal glucosylceramidase (GBA1, a retaining & beta;-glucosidase) or GH31 lysosomal retaining & alpha;-glucosidase (GAA). FluoPol-ABPP screening of our in-house 358-member iminosugar library yielded compound classes selective for either of these enzymes. In particular, we identified a class of N-alkyldeoxynojirimycins that inhibit GAA, but not GBA1, and that may form the starting point for the development of pharmacological chaperone therapeutics for the lysosomal glycogen storage disease that results from genetic deficiency in GAA: Pompe disease. Show less
Fluorescence polarisation activity-based protein profiling for the identification of deoxynojirimycin-type inhibitors selective for lysosomal retaining alpha- and beta-glucosidases
Gracht, D. van der; Rowland, R.J.; Roig-Zamboni, V.; Ferraz, M.J.; Louwerse, M.; Geurink, P.P.; ... ; Artola, M. 2023
Fluorescence polarisation activity-based protein profiling for the identification of deoxynojirimycin-type inhibitors selective for lysosomal retaining alpha- and beta-glucosidases
Article / Letter to editor
open access
Lysosomal exoglycosidases are responsible for processing endocytosed glycans from the non-reducing end to produce the corresponding monosaccharides. Genetic mutations in a particular lysosomal... Show moreLysosomal exoglycosidases are responsible for processing endocytosed glycans from the non-reducing end to produce the corresponding monosaccharides. Genetic mutations in a particular lysosomal glycosidase may result in accumulation of its particular substrate, which may cause diverse lysosomal storage disorders. The identification of effective therapeutic modalities to treat these diseases is a major yet poorly realised objective in biomedicine. One common strategy comprises the identification of effective and selective competitive inhibitors that may serve to stabilize the proper folding of the mutated enzyme, either during maturation and trafficking to, or residence in, endo-lysosomal compartments. The discovery of such inhibitors is greatly aided by effective screening assays, the development of which is the focus of the here-presented work. We developed and applied fluorescent activity-based probes reporting on either human GH30 lysosomal glucosylceramidase (GBA1, a retaining β-glucosidase) or GH31 lysosomal retaining α-glucosidase (GAA). FluoPol-ABPP screening of our in-house 358-member iminosugar library yielded compound classes selective for either of these enzymes. In particular, we identified a class of N-alkyldeoxynojirimycins that inhibit GAA, but not GBA1, and that may form the starting point for the development of pharmacological chaperone therapeutics for the lysosomal glycogen storage disease that results from genetic deficiency in GAA: Pompe disease. Show less
Glycoprotein non-metastatic protein B (GPNMB) plasma values in patients with chronic visceral acid sphingomyelinase deficiency
Eskes, E.C.B; Lienden, M.J.C. van der; Sjouke, B.; Vliet, L. van; Brands, M.M.M.G.; Hollak, C.E.M.; Aerts, J.M.F.G. 2023
Glycoprotein non-metastatic protein B (GPNMB) plasma values in patients with chronic visceral acid sphingomyelinase deficiency
Article / Letter to editor
open access
2024-02-02T00:00:00Z
Acid sphingomyelinase deficiency (ASMD) is a rare LSD characterized by lysosomal accumulation of sphingomyelin, primarily in macrophages. With the recent availability of enzyme replacement therapy,... Show moreAcid sphingomyelinase deficiency (ASMD) is a rare LSD characterized by lysosomal accumulation of sphingomyelin, primarily in macrophages. With the recent availability of enzyme replacement therapy, the need for biomarkers to assess severity of disease has increased. Glycoprotein non-metastatic protein B (GPNMB) plasma levels were demonstrated to be elevated in Gaucher disease. Given the similarities between Gaucher disease and ASMD, the hypothesis was that GPNMB might be a potential biochemical marker for ASMD as well. Plasma samples of ASMD patients were analyzed and GPNMB plasma levels were compared to those of healthy volunteers. Visceral disease severity was classified as severe when splenic, hepatic and pulmonary manifestations were all present and as mild to moderate if this was not the case. Median GPNMB levels in 67 samples of 19 ASMD patients were 185 ng/ml (range 70-811 ng/ml) and were increased compared to 10 healthy controls (median 36 ng/ml, range 9-175 ng/ml, p < 0.001). Median plasma GPNMB levels of ASMD patients with mild to moderate visceral disease compared to patients with severe visceral disease differed significantly and did not overlap (respectively 109 ng/ml, range 70-304 ng/ml and 325 ng/ml, range 165-811 ng/ml, p < 0.001). Correlations with other biochemical markers of ASMD (i.e. chitotriosidase activity, CCL18 and lysosphingomyelin, respectively R = 0.28, p = 0.270; R = 0.34, p = 0.180; R = 0.39, p = 0.100) and clinical parameters (i.e. spleen volume, liver volume, diffusion capacity and forced vital capacity, respectively R = 0.59, p = 0.061, R = 0.5, p = 0.100, R = 0.065, p = 0.810, R = -0.38, p = 0.160) could not be established within this study. The results of this study suggest that GPNMB might be suitable as a biomarker of visceral disease severity in ASMD. Correlations between GPNMB and biochemical or clinical markers of ASMD and response to therapy have to be studied in a larger cohort. Show less
Gaucher disease protects against tuberculosis
Fan, J.; Hale V.L.; Lelieveld, L.T.; Whitworth, L.J.; Busch-Nentwich, E.M.; Troll, M.; ... ; Ramakrishnan, L. 2023
Gaucher disease protects against tuberculosis
Article / Letter to editor
open access
a-Synuclein and lipids in erythrocytes of Gaucher disease carriers and patients before and after enzyme replacement therapy
Moraitou, M.; Sotiroudis, G.; Papagiannakis, N.; Ferraz, M.J.; Xenakis, A.; Aerts, J.M.F.G.; ... ; Michelakakis, H. 2023
a-Synuclein and lipids in erythrocytes of Gaucher disease carriers and patients before and after enzyme replacement therapy
Article / Letter to editor
open access
It is well established that patients with Gaucher disease, as well as carriers of the disease have an increased risk for developing Parkinson's disease. A plethora of evidence suggests that... Show moreIt is well established that patients with Gaucher disease, as well as carriers of the disease have an increased risk for developing Parkinson's disease. A plethora of evidence suggests that disturbed alpha-Synuclein homeostasis is the link between Gaucher disease and Parkinson's disease. The pathogenic mechanism linking these entities is still a topic of debate and both gain- and loss-of-function theories have been put forward, which however are not mutually exclusive. In the present study we expanded our previous studies to include not only Gaucher disease patients but also Gaucher disease carriers and Gaucher disease patients following Enzyme Replacement Therapy. In these groups we investigated alpha-Synuclein in red blood cell membranes in association with lipid abnormalities described in Gaucher disease. These included glucosylceramide and its species, glucosylsphingosine, glucosylcholesterol and plasmalogens. Increased oligomerization of alpha-Synuclein in red blood cell membranes was observed not only in Gaucher disease patients but also in carriers of the disease. There were no qualitative differences in the lipids identified in the groups studied. However, significant quantitative differences compared to controls were observed in Gaucher disease patients but not in Gaucher disease carriers. Enzyme Replacement Therapy reversed the biochemical defects and normalized alpha-Synuclein homeostasis, providing for the first time evidence in human subjects that such homeostatic dysregulation is reversible. Further studies investigating alpha-Synuclein status during the differentiation of erythroid progenitors could provide new data on the pathogenic mechanism of alpha-Synuclein oligomerization in this system. Show less
Corrigendum
Su, Q.; Schroder, S.P.; Lelieveld, L.T.; Guimaraes Da Lomba Ferraz, M.J.; Verhoek, M.; Boot, R.G.; ... ; Kuo, C.L. 2023
Corrigendum: xylose-configured cyclophellitols as selective inhibitors for glucocerebrosidase
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Corrigendum: Xylose-configured cyclophellitols as selective inhibitors for glucocerebrosidase
Su, Q.; Schroder, S.P.; Lelieveld, L.T.; Guimaraes Da Lomba Ferraz, M.J.; Verhoek, M.; Boot, R.G.; ... ; Kuo, C.-L. 2023
Corrigendum: Xylose-configured cyclophellitols as selective inhibitors for glucocerebrosidase
Article / Letter to editor
open access
2023-08-02T00:00:00Z

Lipase-mediated selective hydrolysis of lipid droplets in phase separated-liposomes
Papadopoulou, P.; Pol, R. van der; Hilten, N. van; Moradi, M.A.; Ferraz, M.J.; Aerts, J.M.F.G.; ... ; Kros A. 2023
Lipase-mediated selective hydrolysis of lipid droplets in phase separated-liposomes
Research paper
open access
Corrigendum: Xylose-configured cyclophellitols as selective inhibitors for glucocerebrosidase
Su, Q.; Schröder, S.P.; Lelieveld, L.T.; Guimaraes Da Lomba Ferraz M.J.; Verhoek, M.; Boot, R.G.; ... ; Kuo, C.L. 2022
Corrigendum: Xylose-configured cyclophellitols as selective inhibitors for glucocerebrosidase
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1,6-epi-Cyclophellitol cyclosulfamidate is a bona fide lysosomal α-glucosidase stabilizer for the treatment of Pompe disease
Kok, K.; Kuo, C.L.; Katzy, R.E.; Lelieveld, L.T.; Wu, L.; Roig-Zamboni, V.; ... ; Artola Perez de Azanza, M.E. 2022
1,6-epi-Cyclophellitol cyclosulfamidate is a bona fide lysosomal α-glucosidase stabilizer for the treatment of Pompe disease
Article / Letter to editor
open access
α-Glucosidase inhibitors are potential therapeutics for the treatment of diabetes, viral infections, and Pompe disease. Herein, we report a 1,6-epi-cyclophellitol cyclosulfamidate as a new class of... Show moreα-Glucosidase inhibitors are potential therapeutics for the treatment of diabetes, viral infections, and Pompe disease. Herein, we report a 1,6-epi-cyclophellitol cyclosulfamidate as a new class of reversible α-glucosidase inhibitors that displays enzyme inhibitory activity by virtue of its conformational mimicry of the substrate when bound in the Michaelis complex. The α-d-glc-configured cyclophellitol cyclosulfamidate 4 binds in a competitive manner the human lysosomal acid α-glucosidase (GAA), ER α-glucosidases, and, at higher concentrations, intestinal α-glucosidases, displaying an excellent selectivity over the human β-glucosidases GBA and GBA2 and glucosylceramide synthase (GCS). Cyclosulfamidate 4 stabilizes recombinant human GAA (rhGAA, alglucosidase alfa, Myozyme) in cell medium and plasma and facilitates enzyme trafficking to lysosomes. It stabilizes rhGAA more effectively than existing small-molecule chaperones and does so in vitro, in cellulo, and in vivo in zebrafish, thus representing a promising therapeutic alternative to Miglustat for Pompe disease. Show less
In situ glucosylceramide synthesis and its pharmacological inhibition analysed in cells by 13C5-sphingosine precursor feeding and mass spectrometry
Katzy, R.E.; Guimaraes Da Lomba Ferraz, M.J.; Hazeu, M.D.; Overkleeft, H.S.; Aerts, J.M.F.G. 2022
In situ glucosylceramide synthesis and its pharmacological inhibition analysed in cells by 13C5-sphingosine precursor feeding and mass spectrometry
Article / Letter to editor
open access
Glycosphingolipids (GSLs) fulfil diverse functions in cells. Abnormalities in their metabolism are associated with specific pathologies and, consequently, the pharmacological modulation of GSLs is... Show moreGlycosphingolipids (GSLs) fulfil diverse functions in cells. Abnormalities in their metabolism are associated with specific pathologies and, consequently, the pharmacological modulation of GSLs is considered a therapeutic avenue. The accurate measurement of in situ metabolism of GSLs and the modulatory impact of drugs is warranted. Employing synthesised sphingosine and sphinganine containing C-13 atoms, we developed a method to monitor the de novo synthesis of glucosylceramide, the precursor of complex GSLs, by the enzyme glucosylceramide synthase (GCS). We show that feeding cells with isotope-labelled precursor combined with liquid chromatography-mass spectrometry (MS)/MS analysis allows accurate determination of the IC50 values of therapeutically considered inhibitors (iminosugars and ceramide mimics) of GCS in cultured cells. Acquired data were comparable to those obtained with an earlier method using artificial fluorescently labelled ceramide to feed cells. Show less
Current methods to analyze lysosome morphology, positioning, motility and function
Barral, D.C.; Staiano, L.; Almeida, C.G.; Cutler, D.F.; Eden, E.R.; Futter, C.E.; ... ; Seabra, M.C. 2022
Current methods to analyze lysosome morphology, positioning, motility and function
Article / Letter to editor
open access
Since the discovery of lysosomes more than 70 years ago, much has been learned about the functions of these organelles. Lysosomes were regarded as exclusively degradative organelles, but more... Show moreSince the discovery of lysosomes more than 70 years ago, much has been learned about the functions of these organelles. Lysosomes were regarded as exclusively degradative organelles, but more recent research has shown that they play essential roles in several other cellular functions, such as nutrient sensing, intracellular signalling and metabolism. Methodological advances played a key part in generating our current knowledge about the biology of this multifaceted organelle. In this review, we cover current methods used to analyze lysosome morphology, positioning, motility and function. We highlight the principles behind these methods, the methodological strategies and their advantages and limitations. To extract accurate information and avoid misinterpretations, we discuss the best strategies to identify lysosomes and assess their characteristics and functions. With this review, we aim to stimulate an increase in the quantity and quality of research on lysosomes and further ground-breaking discoveries on an organelle that continues to surprise and excite cell biologists. Show less
HEPES‐buffering of bicarbonate‐containing culture medium perturbs lysosomal glucocerebrosidase activity
Lienden, M.J.C. van der; Aten, J.; Boot, R.G.; Eijk, M.C. van; Aerts, J.M.F.G.; Kuo, C.L. 2022
HEPES‐buffering of bicarbonate‐containing culture medium perturbs lysosomal glucocerebrosidase activity
Article / Letter to editor
open access
Glucocerebrosidase (GCase), encoded by the GBA gene, degrades the ubiquitous glycosphingolipid glucosylceramide. Inherited GCase deficiency causes Gaucher disease (GD). In addition, carriers of an... Show moreGlucocerebrosidase (GCase), encoded by the GBA gene, degrades the ubiquitous glycosphingolipid glucosylceramide. Inherited GCase deficiency causes Gaucher disease (GD). In addition, carriers of an abnormal GBA allele are at increased risk for Parkinson's disease. GCase undergoes extensive modification of its four N-glycans en route to and inside the lysosome that is reflected in changes in molecular weight as detected with sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Fluorescent activity-based probes (ABPs) that covalently label GCase in reaction-based manner in vivo and in vitro allow sensitive visualization of GCase molecules. Using these ABPs, we studied the life cycle of GCase in cultured fibroblasts and macrophage-like RAW264.7 cells. Specific attention was paid to the impact of 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) supplementation to bicarbonate-buffered medium. Here, we report how HEPES-buffered medium markedly influences processing of GCase, its lysosomal degradation, and the total cellular enzyme level. HEPES-containing medium was also found to reduce maturation of other lysosomal enzymes (alpha-glucosidase and beta-glucuronidase) in cells. The presence of HEPES in bicarbonate containing medium increases GCase activity in GD-patient derived fibroblasts, illustrating how the supplementation of HEPES complicates the use of cultured cells for diagnosing GD. Show less
Consequences of excessive glucosylsphingosine in glucocerebrosidase-deficient zebrafish
Lelieveld, L.T.; Gerhardt, S.; Maas, S.; Zwiers, K.C.; Wit, C. de; Beijk, E.H.; ... ; Aerts, J.M.F.G. 2022
Consequences of excessive glucosylsphingosine in glucocerebrosidase-deficient zebrafish
Article / Letter to editor
open access
In Gaucher disease (GD), the deficiency of glucocerebrosidase causes lysosomal accumulation of glucosylceramide (GlcCer), which is partly converted by acid ceramidase to glucosylsphingosine (GlcSph... Show moreIn Gaucher disease (GD), the deficiency of glucocerebrosidase causes lysosomal accumulation of glucosylceramide (GlcCer), which is partly converted by acid ceramidase to glucosylsphingosine (GlcSph) in the lysosome. Chronically elevated blood and tissue GlcSph is thought to contribute to symptoms in GD patients as well as to increased risk for Parkinson's disease. On the other hand, formation of GlcSph may be beneficial since the water soluble sphingoid base is excreted via urine and bile. To study the role of excessive GlcSph formation during glucocerebrosidase deficiency, we studied zebrafish that have two orthologs of acid ceramidase, Asah1a and Asah1b. Only the latter is involved in the formation of GlcSph in glucocerebrosidase-deficient zebrafish as revealed by knockouts of Asah1a or Asah1b with glucocerebrosidase deficiency (either pharmacologically induced or genetic). Comparison of zebrafish with excessive GlcSph (gba1-/- fish) and without GlcSph (gba1-/-:asah1b-/- fish) allowed us to study the consequences of chronic high levels of GlcSph. Prevention of excessive GlcSph in gba1-/-:asah1b-/- fish did not restrict storage cells, GlcCer accumulation, or neuroinflammation. However, GD fish lacking excessive GlcSph show an ameliorated course of disease reflected by significantly increased lifespan, delayed locomotor abnormality, and delayed development of an abnormal curved back posture. The loss of tyrosine hydroxylase 1 (th1) mRNA, a marker of dopaminergic neurons, is slowed down in brain of GD fish lacking excessive GlcSph. In conclusion, in the zebrafish GD model, excess GlcSph has little impact on (neuro)inflammation or the presence of GlcCer-laden macrophages but rather seems harmful to th1-positive dopaminergic neurons. Show less
Real‐Time NMR recording of fermentation and lipid metabolism processes in live microalgae cells
Nami, F.; Joao Ferraz, M.; Bakkum, T.; Aerts, J.M.F.G.; Pandit, A. 2022
Real‐Time NMR recording of fermentation and lipid metabolism processes in live microalgae cells
Article / Letter to editor
open access
Non-invasive and real-time recording of processes in living cells has been limited to detection of small cellular components such as soluble proteins and metabolites. Here we report a multiphase... Show moreNon-invasive and real-time recording of processes in living cells has been limited to detection of small cellular components such as soluble proteins and metabolites. Here we report a multiphase NMR approach using Magic-Angle Spinning NMR to synchronously follow microbial processes of fermentation, lipid metabolism and structural dynamic changes in live microalgae cells. Chlamydomonas reinhardtii green algae were highly concentrated, introducing dark fermentation and anoxia conditions. Single-pulse NMR experiments were applied to obtain temperature-dependent kinetic profiles of the formed fermentation products. Through dynamics-based spectral editing NMR, simultaneous conversion of galactolipids into TAG and free fatty acids was observed and rapid loss of rigid lipid structures. This suggests that lipolysis under dark and anoxia conditions finally results in the breakdown of cell and organelle membranes, which could be beneficial for recovery of intracellular microbial useful products. Show less
Synthesis of broad-specificity activity-based probes for exo-beta-mannosidases
McGregor, N.G.S.; Kuo, C.L.; Beenakker, T.J.M.; Wong, C.S.; Offen, W.A.; Armstrong, Z.W.B.; ... ; Davies, G.J. 2021
Synthesis of broad-specificity activity-based probes for exo-beta-mannosidases
Article / Letter to editor
open access
Exo-beta-mannosidases are a broad class of stereochemically retaining hydrolases that are essential for the breakdown of complex carbohydrate substrates found in all kingdoms of life. Yet the... Show moreExo-beta-mannosidases are a broad class of stereochemically retaining hydrolases that are essential for the breakdown of complex carbohydrate substrates found in all kingdoms of life. Yet the detection of exo-beta-mannosidases in complex biological samples remains challenging, necessitating the development of new methodologies. Cyclophellitol and its analogues selectively label the catalytic nucleophiles of retaining glycoside hydrolases, making them valuable tool compounds. Furthermore, cyclophellitol can be readily redesigned to enable the incorporation of a detection tag, generating activity-based probes (ABPs) that can be used to detect and identify specific glycosidases in complex biological samples. Towards the development of ABPs for exo-beta-mannosidases, we present a concise synthesis of beta-manno-configured cyclophellitol, cyclophellitol aziridine, and N-alkyl cyclophellitol aziridines. We show that these probes covalently label exo-beta-mannosidases from GH families 2, 5, and 164. Structural studies of the resulting complexes support a canonical mechanism-based mode of action in which the active site nucleophile attacks the pseudoanomeric centre to form a stable ester linkage, mimicking the glycosyl enzyme intermediate. Furthermore, we demonstrate activity-based protein profiling using an N-alkyl aziridine derivative by specifically labelling MANBA in mouse kidney tissue. Together, these results show that synthetic manno-configured cyclophellitol analogues hold promise for detecting exo-beta-mannosidases in biological and biomedical research. Show less
The uncovered function of the Drosophila GBA1a-encoded protein
Cabasso, O.; Paul, S.; Maor, G.; Pasmanik-Chor, M.; Kallemeijn, W.W.; Aerts, J.M.F.G.; Horowitz, M. 2021
The uncovered function of the Drosophila GBA1a-encoded protein
Article / Letter to editor
open access

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