The basic objective in our lab has been to study the molecular and cellular mechanism involved in neuronal death, as a direct approach for the understanding of neurodegenerative diseases. Although neuronal death in neurodegenerative diseases is very complex, it seems that certain characteristics are common between them. For example, it seems quite clear that apoptosis contributes to cell death observed in Alzheimer, Parkinson or Hungtinton diseases. We are focused in the study of regulation of neuronal apoptosis. Two questions are being addressed in the lab? 1.- Which is the role of apoptosis in cerebral ischemia-mediated cell death 2.- How synaptic activity and some extracellular factors are able to reduce neuronal apoptosis in neurodegenerative diseases?
Role of apoptosis in cerebral ischemia-mediated cell death
Stroke is a brain injury caused by decreased blood supply to the brain. The deprivation of oxygen and glucose (OGD) in the ischemic brain eventually leads to cell death which was believed to have necrotic features. Over the last decade this view has been challenged. Mounting evidences indicate the appearance of active caspases in the ischemic brain tissue or in cultured cortical neurons transiently deprived of oxygen and glucose, suggesting that the loss of neurons by apoptosis might be important, particularly in the penumbra area. Several factors are believed to contribute to ischemic brain injury. An increase in glutamate release seems to be a major cause in triggering cellular death, although several other factors such as cytokines could also play an important role. We are interested in the contribution of death receptors, its signalling pathways and ER stress in ischemia-mediated apoptosis.
Inhibition of neuronal apoptosis by synaptic activity and extracellular factors
The molecular mechanisms underlying Alzheimer disease-induced synaptic dysfunction, memory loss and neurodegeneration of specific neuronal populations are largely unknown. It has been described that loss of synaptic activity could trigger neurnal apoptosis and also it is known that A? is able to inhibit excitatory neurotransmision. We believe that the maintenance of excitatory neurotransmission could prevent neuronal apoptosis asociated to Alzheimer and other neurodegenerative diseases. In our lab, we have demostrated that stimulation of NMDA receptors is able to produce a long-term protection of cerebellar granule cells from apoptosis mediated by synaptic activity withdrawal by a mechanism that produces the inhibition of caspases and the JNK kinases in a PI3k/Akt pathway dependent way. Also an increase in XIAP expression is observed. We are interested in checking the expression levels of IAPs, the signaling pathways activated by survival growth factors that regulate the expression and activity of IAPs and the neuroprotective role of IAPs in Alzheimer´s disease models (brain and primary neurons of APP Tg mice and ?-amiloid treated cortical neurons).
SCOPUS Base de dades científica
JCR Word Base de dades científica
Web of Sciences Base de dades científica
CONTACTA AMB NOSALTRES
Departament de Bioquímica i Biologia Molecular
Facultat de Medicina
08193 Bellaterra (Cerdanyola del Vallès)
+34 93 581 19 10
+34 93 581 25 77