Publications by authors named "F Shishido"
Article Synopsis
- Hereditary spastic paraplegia (HSP) is a neurological condition with various forms, and SPG26 is a more complex type that involves difficulty with movement, cognitive issues, and other neurological symptoms due to mutations in the GM2S gene.
- This study identified a new genetic variant in a Japanese patient with SPG26, which led to the finding that their cells had impaired ganglioside expression, and laboratory tests confirmed that the variant protein lacked the expected enzyme activity.
- The research also discovered additional potentially harmful genetic variants through analysis of a population database, underscoring the need for further molecular studies on HSP26-related mutations in Japan.
Article Synopsis
- ST3GAL5 is a gene responsible for producing GM3 synthase, crucial for synthesizing GM3, a ganglioside involved in brain function; deficiencies in this enzyme lead to GM3 synthase deficiency (GM3SD).
- Two siblings with GM3SD were identified through whole-exome sequencing, revealing novel pathogenic variants and presenting symptoms like irritability, growth failure, developmental delays, and severe neurological issues.
- Diagnosing GM3SD outside the Amish population is uncommon and may require advanced genetic testing; while there’s no established treatment, deep brain stimulation shows promise for managing specific symptoms like involuntary movements.
GM3 synthase (GM3S) is a sialyltransferase that transfers sialic acid from CMP-sialic acid to lactosylceramide. This reaction results in formation of ganglioside GM3 and is essential for biosynthesis of its downstream derivatives, which include a- and b-series gangliosides. Here, we describe a method for GM3S enzymatic assay using fluorescence-labeled alkyl lactoside as acceptor substrate, followed by HPLC for separation of enzymatic product.
View Article and Find Full Text PDFGM3, a precursor for synthesis of a- and b-series gangliosides, is elevated in adipocytes of obese model animals and in sera of obese human patients with type 2 diabetes and/or dyslipidemia. GM3 synthase (GM3S)-KO C57BL/6 mice display enhanced insulin sensitivity and reduced development of high-fat diet-induced insulin resistance. However, the pathophysiological roles of GM3 and related gangliosides in the central control of feeding and metabolism remain unclear.
View Article and Find Full Text PDFSince the successful molecular cloning in 1998 of GM3 synthase (GM3S, ST3GAL5), the enzyme responsible for initiating biosynthesis of all complex gangliosides, the efforts of our research group have been focused on clarifying the physiological and pathological implications of gangliosides, particularly GM3. We have identified isoforms of GM3S proteins having distinctive lengths of N-terminal cytoplasmic tails, and found that these cytoplasmic tails define subcellular localization, stability, and in vivo activity of GM3S isoforms. Our studies of the molecular pathogenesis of type 2 diabetes, focused on interaction between insulin receptor and GM3 in membrane microdomains, led to a novel concept: type 2 diabetes and certain other lifestyle-related diseases are membrane microdomain disorders resulting from aberrant expression of gangliosides.
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