scholarly journals Glycogen metabolism in tissues from a mouse model of Lafora disease

2007 ◽  
Vol 457 (2) ◽  
pp. 264-269 ◽  
Author(s):  
Wei Wang ◽  
Hannes Lohi ◽  
Alexander V. Skurat ◽  
Anna A. DePaoli-Roach ◽  
Berge A. Minassian ◽  
...  
Keyword(s):  
Mouse Model ◽  
Glycogen Metabolism ◽  
Lafora Disease

Astrocytic glycogen accumulation drives the pathophysiology of neurodegeneration in Lafora disease

Brain ◽  
2021 ◽  
Author(s):  
Jordi Duran ◽  
Arnau Hervera ◽  
Kia H Markussen ◽  
Olga Varea ◽  
Iliana López-Soldado ◽  
...  
Keyword(s):  
Mouse Model ◽  
Neurodegenerative Disorder ◽  
Glycogen Synthase ◽  
Glycogen Synthesis ◽  
Glycogen Metabolism ◽  
Cell Type ◽  
Lafora Disease ◽  
Glycogen Accumulation ◽  
Lafora Bodies

Abstract The hallmark of Lafora disease, a fatal neurodegenerative disorder, is the accumulation of intracellular glycogen aggregates, called Lafora bodies. Until recently, it was widely believed that brain Lafora bodies were present exclusively in neurons and thus that Lafora disease pathology derived from their accumulation in this cell population. However, recent evidence indicates that Lafora bodies are also present in astrocytes. To define the role of astrocytic Lafora bodies in Lafora disease pathology, we deleted glycogen synthase specifically from astrocytes in a mouse model of the disease (malinKO). Strikingly, blocking glycogen synthesis in astrocytes—thus impeding Lafora bodies accumulation in this cell type—prevented the increase in neurodegeneration markers, autophagy impairment, and metabolic changes characteristic of the malinKO model. Conversely, mice that overaccumulate glycogen in astrocytes showed an increase in these markers. These results unveil the deleterious consequences of the deregulation of glycogen metabolism in astrocytes and change the perspective that Lafora disease is caused solely by alterations in neurons.

scholarly journals Inhibiting glycogen synthesis prevents lafora disease in a mouse model

2013 ◽  
pp. n/a-n/a ◽  
Author(s):  
Bartholomew A Pederson ◽  
Julie Turnbull ◽  
Jonathan R Epp ◽  
Staci A Weaver ◽  
Xiaochu Zhao ◽  
...  
Keyword(s):  
Mouse Model ◽  
Glycogen Synthesis ◽  
Lafora Disease

scholarly journals In vivo glutamate clearance defects in a mouse model of Lafora disease

2019 ◽  
Vol 320 ◽  
pp. 112959 ◽  
Author(s):  
C. Muñoz-Ballester ◽  
N. Santana ◽  
E. Perez-Jimenez ◽  
R. Viana ◽  
F. Artigas ◽  
...  
Keyword(s):  
Mouse Model ◽  
Lafora Disease

scholarly journals Pharmacological Interventions to Ameliorate Neuropathological Symptoms in a Mouse Model of Lafora Disease

2015 ◽  
Vol 53 (2) ◽  
pp. 1296-1309 ◽  
Author(s):  
Arnaud Berthier ◽  
Miguel Payá ◽  
Ana M. García-Cabrero ◽  
Maria Inmaculada Ballester ◽  
Miguel Heredia ◽  
...  
Keyword(s):  
Mouse Model ◽  
Lafora Disease ◽  
Pharmacological Interventions

scholarly journals Laforin, a dual-specificity phosphatase involved in Lafora disease, is phosphorylated at Ser25 by AMP-activated protein kinase

2011 ◽  
Vol 439 (2) ◽  
pp. 265-275 ◽  
Author(s):  
Carlos Romá-Mateo ◽  
Maria del Carmen Solaz-Fuster ◽  
José Vicente Gimeno-Alcañiz ◽  
Vikas V. Dukhande ◽  
Jordi Donderis ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Neurodegenerative Disorder ◽  
Critical Role ◽  
Glycogen Metabolism ◽  
Lafora Disease ◽  
Gene Encoding ◽  
Dual Specificity Phosphatase ◽  
Progressive Myoclonus Epilepsy ◽  
Dual Specificity ◽  
Amp Activated Protein Kinase

Lafora progressive myoclonus epilepsy [LD (Lafora disease)] is a fatal autosomal recessive neurodegenerative disorder caused by loss-of-function mutations in either the EPM2A gene, encoding the dual-specificity phosphatase laforin, or the EPM2B gene, encoding the E3-ubiquitin ligase malin. Previously, we and others showed that laforin and malin form a functional complex that regulates multiple aspects of glycogen metabolism, and that the interaction between laforin and malin is enhanced by conditions activating AMPK (AMP-activated protein kinase). In the present study, we demonstrate that laforin is a phosphoprotein, as indicated by two-dimensional electrophoresis, and we identify Ser25 as the residue involved in this modification. We also show that Ser25 is phosphorylated both in vitro and in vivo by AMPK. Lastly, we demonstrate that this residue plays a critical role for both the phosphatase activity and the ability of laforin to interact with itself and with previously established binding partners. The results of the present study suggest that phosphorylation of laforin-Ser25 by AMPK provides a mechanism to modulate the interaction between laforin and malin. Regulation of this complex is necessary to maintain normal glycogen metabolism. Importantly, Ser25 is mutated in some LD patients (S25P), and our results begin to elucidate the mechanism of disease in these patients.

scholarly journals Defining the Tetramodular Dimer Structure of Laforin in Glycogen Metabolism and Lafora Disease

2015 ◽  
Vol 29 (S1) ◽  
Author(s):  
M Kathryn Brewer ◽  
Madushi Raththagala ◽  
Matthew Parker ◽  
Lance Hellman ◽  
Ben Turner ◽  
...  
Keyword(s):  
Glycogen Metabolism ◽  
Lafora Disease ◽  
Dimer Structure

Ppp1r3d deficiency preferentially inhibits neuronal and cardiac Lafora body formation in a mouse model of the fatal epilepsy Lafora disease

2020 ◽  
Author(s):  
Lori Israelian ◽  
Silvia Nitschke ◽  
Peixiang Wang ◽  
Xiaochu Zhao ◽  
Ami M. Perri ◽  
...  
Keyword(s):  
Mouse Model ◽  
Lafora Disease ◽  
Body Formation ◽  
Lafora Body

Transcriptional profiling of a mouse model for Lafora disease reveals dysregulation of genes involved in the expression and modification of proteins

2005 ◽  
Vol 387 (2) ◽  
pp. 62-67 ◽  
Author(s):  
Subramaniam Ganesh ◽  
Naomi Tsurutani ◽  
Kenji Amano ◽  
Shuchi Mittal ◽  
Chiharu Uchikawa ◽  
...  
Keyword(s):  
Mouse Model ◽  
Transcriptional Profiling ◽  
Lafora Disease
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