Navigation Links
A mouse model brings new perspectives on Lafora disease

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
Institute for Research in Biomedicine (IRB Barcelona)

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:
(Date:11/25/2015)... , Nov. 25, 2015 /PRNewswire/ - Aeterna Zentaris ... that its business and prospects remain fundamentally strong ... Zoptrex™ (zoptarelin doxorubicin) recently received DSMB recommendation to ... completion following review of the final interim efficacy ... 2 Primary Endpoint in men with heavily pretreated ...
(Date:11/25/2015)... ... November 25, 2015 , ... Jessica ... on AngelList early in their initial angel funding process. Now, they are paying ... looking to make early stage investments in the microbiome space. In this, ...
(Date:11/24/2015)... Therapeutics, Inc. (NASDAQ: HALO ) will be presenting at the ... on Wednesday, December 2 at 9:30 a.m. ET/6:30 a.m. PT . ... a corporate overview. th Annual Oppenheimer Healthcare Conference ... a.m. PT . Jim Mazzola , vice president of ... --> th Annual Oppenheimer Healthcare Conference in ...
(Date:11/24/2015)... - Aeterna Zentaris Inc. (NASDAQ:  AEZS) (TSX: AEZ) (the "Company"), ... Toronto Stock Exchange, confirms that as of the date ... that would cause the recent movements in the Company,s ... About Aeterna Zentaris Inc. . ... Zentaris is a specialty biopharmaceutical company engaged in developing ...
Breaking Biology Technology:
(Date:11/2/2015)... , Nov. 2, 2015  SRI International has ... to provide preclinical development services to the National Cancer ... SRI will provide scientific expertise, modern testing and support ... of preclinical pharmacology and toxicology studies to evaluate potential ... --> The PREVENT Cancer Drug Development Program is ...
(Date:10/29/2015)... 2015 Daon, a global leader in mobile ... a new version of its IdentityX Platform , ... America have already installed IdentityX v4.0 and ... FIDO UAF certified server component as an ... FIDO features. These customers include some of the largest ...
(Date:10/29/2015)... 2015 NXTD ) ("NXT-ID" ... on the growing mobile commerce market and creator ... a leading marketplace to discover and buy innovative ... wallet on StackSocial for this holiday season.   ... "Company"), a biometric authentication company focused on the ...
Breaking Biology News(10 mins):