From glycogen metabolism to Lafora disease

Glycogen synthesis is normally absent in neurons. However, inclusion bodies resembling abnormal glycogen accumulate in several neurological diseases, particularly in progressive myoclonus epilepsy or Lafora disease. In this conference recent advances in this research topic will be presented and discussed.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

Estudi d’estratègies de clipping per a modulacions OFDM

En el treball s’analitzen diferents mètodes de clipping (retall del senyal) per a un sistema amb transmissió OFDM (Hiperlan type 2), considerant diferents nivells de soroll al canal. L’objectiu del clipping és disminuir efectes deguts a la no-linealitat de l’amplificador de potencia sense necessitat de treballar en excés a la zona lineal (back-off elevat) i així poder estalviar energia i fer que la bateria dels diferents sistemes que utilitzen la modulació especificada duri més. Per a cada una de les simulacions esmentades es monitoritzarà la qualitat de l’enllaç, la disminució de la variança i el comportament del ACPR (Adjacent Channel Power Ratio). Aquests seran els paràmetres de referència per argumentar la utilitat dels sistemes de clipping. Cada una de les simulacions treballarà amb diferents nivells d’IBO per tal de veure la seva resposta en funció de la zona de treball, ja sigui lineal o de saturació. Els resultats mostren que els sistemes de clipping permet disminuir el nivell d’IBO fins al límit de la zona lineal i augmentar el nivell d’ACPR de la transmissió. Aquest fet és impossible d’aconseguir sense l’ús d’aquesta eina disposat que si l’amplificador se satura i crea soroll fora de banda, no el podrem filtrar

Lafora disease offers a unique window into neuronal glycogen metabolism

Lafora disease (LD) is a fatal, autosomal recessive, glycogen-storage disorder that manifests as severe epilepsy. LD results from mutations in the gene encoding either the glycogen phosphatase laforin or the E3 ubiquitin ligase malin. Individuals with LD develop cytoplasmic, aberrant glycogen inclusions in nearly all tissues that more closely resemble plant starch than human glycogen. This Minireview discusses the unique window into glycogen metabolism that LD research offers. It also highlights recent discoveries, including that glycogen contains covalently bound phosphate and that neurons synthesize glycogen and express both glycogen synthase and glycogen phosphorylase

Suppression of glycogen synthesis as a treatment for Lafora disease: Establishing the window of opportunity

Lafora disease (LD) is a fatal adolescence-onset neurodegenerative condition. The hallmark of LD is the accumulation of aberrant glycogen aggregates called Lafora bodies (LBs) in the brain and other tissues. Impeding glycogen synthesis from early embryonic stages by genetic suppression of glycogen synthase (MGS) in an animal model of LD prevents LB formation and ultimately the pathological manifestations of LD thereby indicating that LBs are responsible for the pathophysiology of the disease. However, it is not clear whether eliminating glycogen synthesis in an adult animal after LBs have already formed would halt or reverse the progression of LD. Herein we generated a mouse model of LD with inducible MGS suppression. We evaluated the effect of MGS suppression at different time points on LB accumulation as well as on the appearance of neuroinflammation, a pathologic trait of LD models. In the skeletal muscle, MGS suppression in adult LD mice blocked the formation of new LBs and reduced the number of glycogen aggregates. In the brain, early but not late MGS suppression halted the accumulation of LBs. However, the neuroinflammatory response was still present, as shown by the levels of reactive astrocytes, microglia and inflammatory cytokines. Our results confirm that MGS as a promising therapeutic target for LD and highlight the importance of an early diagnosis for effective treatment of the disease