Navigation Links
A mouse model brings new perspectives on Lafora disease
Date:12/12/2011

Short-term energy storage in animal cells is usually achieved through the accumulation of glucose, in the form of long and branched chains, known as glycogen. But when this accumulation happens in neurons it is fatal, causing them to degenerate. This neuronal deterioration and death associated with glycogen accumulation is the hallmark of an extremely rare and progressive type of epilepsy known as Lafora disease (LD).

The journal EMBO Molecular Medicine has just published online the new insights into LD provided by a team of Spanish researchers headed by Joan J. Guinovart, director of the IRB Barcelona and Professor at the University of Barcelona (UB), in collaboration with Agns Gruart and Jos M. Delgado at the Division of Neurosciences at the Pablo Olavide University in Seville, and Eduardo Soriano, Professor at the UB and researcher at IRB Barcelona.

LD is a fatal, inherited and progressive form of epilepsy that causes irreversible neurodegeneration and for which no cure or effective treatment is available. Onset typically occurs during late childhood or adolescence, generally starting with epileptic seizures, progressing into deterioration of neurological functions. One of the hallmarks of the disease is the abnormal accumulation of glycogen aggregates, known as Lafora bodies (LB), in neurons. In these cells, two genes, malin and laforin, act in unison to block glycogen storage in normal conditions. Mutations changes in DNA in either laforin or malin genes are responsible for this disease.

The group of researchers led by Guinovart has developed a genetically engineered mice line lacking the malin gene, thus mimicking human LD in this animal model. The results obtained confirm the role of the malin-laforin complex in the regulation of glycogen synthesis in neurons. Jordi Duran, first author of the study together with Jordi Valls, explains, "Brain cells control their glycogen levels carefully by employing a 'team of wardens', namely malin and laforin. We now know that when one of these two genes is not active mice develop glycogen aggregates in these cells, which progressively deteriorate and finally die". Since the loss of function of malin induces the accumulation of LB and cell death in neurons in human LD patients and mice, "this model helps us to confirm our hypotheses on the origin of this LD".

Also, "the study provides evidence of the existence of LB in a special type of brain cells, known as inhibitory interneurons". In the complex architecture of the brain, these inhibitory interneurons normally generate 'stop signals' for neural excitation. In this regard, the researchers propose that the higher excitability of neurons and the propensity to epileptic seizures observed in these engineered mice are related to the loss of inhibitory interneurons. Interestingly, decreases in the populations of this cell type occur in some cases of epilepsy, schizophrenia, and some neurodegenerative disorders, such as Alzheimer's.

Scarcely a hundred years have passed since the Spanish neurologist Gonzalo R. Lafora described Lafora bodies. Yet unravelling the origins of LD is on the horizon. A better understanding of the mechanisms that block glycogen accumulation in brain cells will provide new insights towards effective treatments for LD and other neurodegenerative diseases.


'/>"/>

Contact: Nuria Noriega
34-934-037-255
Institute for Research in Biomedicine (IRB Barcelona)
Source:Eurekalert

Related biology technology :

1. ExonHit Launches Mouse Genome SpliceArray(TM) for use in Human Disease Modeling Studies
2. Mouse study reveals genetic component of empathy
3. febit First to Offer Newly Published Mouse Genome on a Chip for DNA/RNA Detection and Enrichment
4. EnVivo Pharmaceuticals Announces Reversal of Cognitive Deficits in Alzheimers Disease Transgenic Mouse Model With Gamma-Secretase Modulator
5. ALPCO Introduces a Mouse HMW and Total Adiponectin ELISA
6. MD Bioproducts Releases a New Mouse T1/ST2 ELISA
7. Crescendo Biologics Announces First Triple Knockout Mouse
8. A knockout resource for mouse genetics
9. Researchers produce detailed map of gene activity in mouse brain
10. Campbell Alliance Sales Practice to Present at CBIs Leadership Summit on Evolving the Pharma Sales Model
11. Repligen Announces Publication of Positive Results with Proprietary HDAC Inhibitor in Huntingtons Disease Model
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:2/8/2016)... 2016 Should antibiotic bone cement products be ... prevent infection after standard total hip or knee replacement ... Institute have been fielding a lot lately. ... Line?" --> "Antibiotic Bone Cement: ... --> While there isn,t a simple answer, ...
(Date:2/8/2016)... , February 8, 2016 ... Oncology Private Limited, an innovation-driven oncology company developing ... and less toxic, today announced that chairman emeritus ... has invested in the company as part of ... round, joining existing investors Navam Capital and Aarin ...
(Date:2/8/2016)... ... February 08, 2016 , ... Thomas ... is the Executive Vice President for Corporate Services and the Chief Financial Officer ... Payable, Payroll, Billing Operations, Treasury, Managed Care Contracting, Supply Chain, and Investments. , ...
(Date:2/8/2016)... Calverton, Maryland (PRWEB) , ... February 08, 2016 , ... ... our BSI Web product. The upgrade represents a completely new technical foundation and ... Engage will offer a responsive design interface, significantly increased speed for search results, a ...
Breaking Biology Technology:
(Date:2/4/2016)... , Feb. 4, 2016 The field ... one of the most popular hubs of the ... and other huge studies of human microbiota, have ... few years, the microbiome space has literally exploded ... research. This report focuses on biomedical aspects ...
(Date:2/2/2016)... 2016  BioMEMS devices deployed in hospitals ... medical screening and diagnostic applications, such as ... that facilitate and assure continuous monitoring without ... being bolstered through new opportunities offered by ... coupled with wireless connectivity and low power ...
(Date:2/2/2016)... 2, 2016  Based on its recent analysis ... recognizes US-based Intelligent Retinal Imaging Systems (IRIS) with ... for New Product Innovation. IRIS, a prominent cloud-based ... America , is poised to set the ... retinopathy market. The IRIS technology presents superior price-performance ...
Breaking Biology News(10 mins):