Browsing by Author "Armstrong, Dustin D."

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    The 5th International Lafora Epilepsy Workshop: Basic science elucidating therapeutic options and preparing for therapies in the clinic
    (Elsevier, 2020-02) Gentry, Matthew S.; Afawi, Zaid; Armstrong, Dustin D.; Delgado-Escueta, Antonio; Goldberg, Y. Paul; Grossman, Tamar R.; Guinovart, Joan J.; Harris, Frank; Hurley, Thomas D.; Michelucci, Roberto; Minassian, Berge A.; Sanz, Pascual; Worby, Carolyn A.; Serratosa, Jose M.; Biochemistry and Molecular Biology, School of Medicine
    Lafora disease (LD) is both a fatal childhood epilepsy and a glycogen storage disease caused by recessive mutations in either the Epilepsy progressive myoclonus 2A (EPM2A) or EPM2B genes. Hallmarks of LD are aberrant, cytoplasmic carbohydrate aggregates called Lafora bodies (LBs) that are a disease driver. The 5th International Lafora Epilepsy Workshop was recently held in Alcala de Henares, Spain. The workshop brought together nearly 100 clinicians, academic and industry scientists, trainees, National Institutes of Health (NIH) representation, and friends and family members of patients with LD. The workshop covered aspects of LD ranging from defining basic scientific mechanisms to elucidating a LD therapy or cure and a recently launched LD natural history study.
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    Brain glycogen serves as a critical glucosamine cache required for protein glycosylation
    (Elsevier, 2021) Sun, Ramon C.; Young, Lyndsay E.A.; Bruntz, Ronald C.; Markussen, Kia H.; Zhou, Zhengqiu; Conroy, Lindsey R.; Hawkinson, Tara R.; Clarke, Harrison A.; Stanback, Alexandra E.; Macedo, Jessica K.A.; Emanuelle, Shane; Brewer, M. Kathryn; Rondon, Alberto L.; Mestas, Annette; Sanders, William C.; Mahalingan, Krishna K.; Tang, Buyun; Chikwana, Vimbai M.; Segvich, Dyann M.; Contreras, Christopher J.; Allenger, Elizabeth J.; Brainson, Christine F.; Johnson, Lance A.; Taylor, Richard E.; Armstrong, Dustin D.; Shaffer, Robert; Waechter, Charles J.; Vander Kooi, Craig W.; DePaoli-Roach, Anna A.; Roach, Peter J.; Hurley, Thomas D.; Drake, Richard R.; Gentry, Matthew S.; Biochemistry and Molecular Biology, School of Medicine
    Glycosylation defects are a hallmark of many nervous system diseases. However, the molecular and metabolic basis for this pathology is not fully understood. In this study, we found that N-linked protein glycosylation in the brain is metabolically channeled to glucosamine metabolism through glycogenolysis. We discovered that glucosamine is an abundant constituent of brain glycogen, which functions as a glucosamine reservoir for multiple glycoconjugates. We demonstrated the enzymatic incorporation of glucosamine into glycogen by glycogen synthase, and the release by glycogen phosphorylase by biochemical and structural methodologies, in primary astrocytes, and in vivo by isotopic tracing and mass spectrometry. Using two mouse models of glycogen storage diseases, we showed that disruption of brain glycogen metabolism causes global decreases in free pools of UDP-N-acetylglucosamine and N-linked protein glycosylation. These findings revealed fundamental biological roles of brain glycogen in protein glycosylation with direct relevance to multiple human diseases of the central nervous system.
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    Targeting Pathogenic Lafora Bodies in Lafora Disease Using an Antibody-Enzyme Fusion
    (Elsevier, 2019-07-25) Brewer, M. Kathryn; Uittenbogaard, Annette; Austin, Grant L.; Segvich, Dyann M.; DePaoli-Roach, Anna; Roach, Peter J.; McCarthy, John J.; Simmons, Zoe R.; Brandon, Jason A.; Zhou, Zhengqiu; Zeller, Jill; Young, Lyndsay E. A.; Sun, Ramon C.; Pauly, James R.; Aziz, Nadine M.; Hodges, Bradley L.; McKnight, Tracy R.; Armstrong, Dustin D.; Gentry, Matthew S.; Biochemistry and Molecular Biology, School of Medicine