ArticleHuman molecular genetics2010
Specific saposin C deficiency: CNS impairment and acid beta-glucosidase effects in the mouse.
Article in Human molecular genetics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 37 citations in OpenAlex.
- Review
- Neuroinflammation in Gaucher disease, neuronal ceroid lipofuscinosis, and commonalities with Parkinson's disease.Brain research · 2022Review
- Systemic enzyme delivery by blood-brain barrier-penetrating SapC-DOPS nanovesicles for treatment of neuronopathic Gaucher disease.EBioMedicine · 2020Article
- Characterization of the visceral and neuronal phenotype of 4L/PS-NA mice modeling Gaucher disease.PloS one · 2020Article
- Acute Gaucher Disease-Like Condition in an Indian Infant with a Novel Biallelic Mutation in the Prosaposin Gene.Journal of pediatric genetics · 2019Article
- Combination of acid β-glucosidase mutation and Saposin C deficiency in mice reveals Gba1 mutation dependent and tissue-specific disease phenotype.Scientific reports · 2019Article
- Exploring genetic modifiers of Gaucher disease: The next horizon.Human mutation · 2018Review
- Molecular regulations and therapeutic targets of Gaucher disease.Cytokine & growth factor reviews · 2018Review
- A saposin deficiency model in Drosophila: Lysosomal storage, progressive neurodegeneration and sensory physiological decline.Neurobiology of disease · 2017Article
- Neuronopathic Gaucher disease: dysregulated mRNAs and miRNAs in brain pathogenesis and effects of pharmacologic chaperone treatment in a mouse model.Human molecular genetics · 2015Article
- Structure of human saposin A at lysosomal pH.Acta crystallographica. Section F, Structural biology communications · 2015Article
- LIMP-2 expression is critical for β-glucocerebrosidase activity and α-synuclein clearance.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Multiple pathogenic proteins implicated in neuronopathic Gaucher disease mice.Human molecular genetics · 2014Article
- Autophagy-lysosome pathway associated neuropathology and axonal degeneration in the brains of alpha-galactosidase A-deficient mice.Acta neuropathologica communications · 2014Article
- Tissue-specific effects of saposin A and saposin B on glycosphingolipid degradation in mutant mice.Human molecular genetics · 2013Article
- GPR37 and GPR37L1 are receptors for the neuroprotective and glioprotective factors prosaptide and prosaposin.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Substrate compositional variation with tissue/region and Gba1 mutations in mouse models--implications for Gaucher disease.PloS one · 2013Article
- The role of saposin C in Gaucher disease.Molecular genetics and metabolism · 2012Review
- Animal models for Gaucher disease research.Disease models & mechanisms · 2011Review
- Article
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Saposins A, B, C and D are derived from a common precursor, prosaposin (psap). The few patients with saposin C deficiency develop a Gaucher disease-like central nervous system (CNS) phenotype attributed to diminished glucosylceramide (GC) cleavage activity by acid beta-glucosidase (GCase). The in vivo effects of saposin C were examined by creating mice with selective absence of saposin C (C-/-) using a knock-in point mutation (cysteine-to-proline) in exon 11 of the psap gene. In C-/- mice, prosaposin and saposins A, B and D proteins were present at near wild-type levels, but the saposin C protein was absent. By 1 year, the C-/- mice exhibited weakness of the hind limbs and progressive ataxia. Decreased neuromotor activity and impaired hippocampal long-term potentiation were evident. Foamy storage cells were observed in dorsal root ganglion and there was progressive loss of cerebellar Purkinje cells and atrophy of cerebellar granule cells. Ultrastructural analyses revealed inclusions in axonal processes in the spinal cord, sciatic nerve and brain, but no excess of multivesicular bodies. Activated microglial cells and astrocytes were present in thalamus, brain stem, cerebellum and spinal cord, indicating regional pro-inflammatory responses. No storage cells were found in visceral organs of these mice. The absence of saposin C led to moderate increases in GC and lactosylceramide (LacCer) and their deacylated analogues. These results support the view that saposin C has multiple roles in glycosphingolipid (GSL) catabolism as well as a prominent function in CNS and axonal integrity independent of its role as an optimizer/stabilizer of GCase.
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