title: Inhibiting glycogen synthesis prevents Lafora disease in a mouse model.
abstract: Lafora disease (LD) is a fatal progressive myoclonus epilepsy characterized neuropathologically by aggregates of abnormally structured glycogen and proteins (Lafora bodies [LBs]), and neurodegeneration. Whether LBs could be prevented by inhibiting glycogen synthesis and whether they are pathogenic remain uncertain. We genetically eliminated brain glycogen synthesis in LD mice. This resulted in long-term prevention of LB formation, neurodegeneration, and seizure susceptibility. This study establishes that glycogen synthesis is requisite for LB formation and that LBs are pathogenic. It opens a therapeutic window for potential treatments in LD with known and future small molecule inhibitors of glycogen synthesis.
authors.affiliation: Indiana University School of Medicine-Muncie, Ball State University, Muncie, IN.
authors.forename: Bartholomew A
authors.initials: BA
authors.lastname: Pederson
authors.forename: Julie
authors.initials: J
authors.lastname: Turnbull
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Epp
authors.forename: Staci A
authors.initials: SA
authors.lastname: Weaver
authors.forename: Xiaochu
authors.initials: X
authors.lastname: Zhao
authors.forename: Nela
authors.initials: N
authors.lastname: Pencea
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Roach
authors.forename: Paul W
authors.initials: PW
authors.lastname: Frankland
authors.forename: Cameron A
authors.initials: CA
authors.lastname: Ackerley
authors.forename: Berge A
authors.initials: BA
authors.lastname: Minassian
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D054637:Dual-Specificity Phosphatases / Q000235:genetics; D055786:Gene Knockout Techniques; D006003:Glycogen / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*; D006006:Glycogen Synthase / Q000235:genetics / Q000378:metabolism; D020192:Lafora Disease / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D054558:Protein Tyrosine Phosphatases, Non-Receptor
chemical_list: D006003:Glycogen; D006006:Glycogen Synthase; D054637:Dual-Specificity Phosphatases; C491989:Epm2a protein, mouse; D054558:Protein Tyrosine Phosphatases, Non-Receptor
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