Structure specificity of ER stress in the Cln8-mnd mouse model of the late-infantile neuronal ceroid. (Contributo in atti di convegno)

Type
Label
  • Structure specificity of ER stress in the Cln8-mnd mouse model of the late-infantile neuronal ceroid. (Contributo in atti di convegno) (literal)
Anno
  • 2008-01-01T00:00:00+01:00 (literal)
Alternative label
  • Guarneri P.; Galizzi G.; Russo D.; Guarneri R.; Cascio C.; Deidda I.; Bigini P.; Mennini T.; Passantino R. (2008)
    Structure specificity of ER stress in the Cln8-mnd mouse model of the late-infantile neuronal ceroid.
    in 6th Forum of European Neuroscience, Ginevra (Svizzera), 12-16 luglio 2008
    (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#autori
  • Guarneri P.; Galizzi G.; Russo D.; Guarneri R.; Cascio C.; Deidda I.; Bigini P.; Mennini T.; Passantino R. (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#altreInformazioni
  • Presente anche in formato digitalizzato (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#titoloVolume
  • 6th Forum of European Neuroscience (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#volumeInCollana
  • FENS Abstr. vol 4, 2008 (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#affiliazioni
  • CNR - Istituto di biomedicina e di immunologia molecolare \"Alberto Monroy\", Palermo, Italia. Istituto di Ricerche Farmacologiche \"Mario Negri\", Milano, Italia (literal)
Titolo
  • Structure specificity of ER stress in the Cln8-mnd mouse model of the late-infantile neuronal ceroid. (literal)
Http://www.cnr.it/ontology/cnr/pubblicazioni.owl#isbn
  • 92-990014-3-X (literal)
Abstract
  • The neuronal ceroid lipofuscinoses (NCLs) are a group of neurodegenerative diseases characterized by the lysosomal accumulation of autofluorescent storage material. They are linked to mutations in at least six genes (CLN1-9) leading to progressive visual loss, dementia, motor decline and epilepsy. The exact pathomechanisms of neurodegeneration of selective CNS structures are still unknown. We investigated whether ER stress is involved in the pathogenesis of the mnd mouse which is a model of a variant form of the late-infantile NCLs, linked to mutation in the CLN8 gene encoding a ER-Golgi protein with unknown function. Markers of ER stress-mediated UPR activation and apoptotic parameters were analyzed in different brain areas and in the retina at the early stage of mnd disease. We found that Grp78/BiP expression was increased in the cerebellum, hippocampus and retina of mnd mice at 1 month, but it was unchanged in the cerebral cortex and spinal cord. The activation of the transcription factor CHOP in the cerebellum and hippocampus was accompanied by a caspase-3 cleavage, whereas, a caspase-12-dependent pathway was activated in the retina. Increases in NF-kB, TRAF2, TNFalpha and TNFR1 in the structures were detected. In the cerebral cortex and spinal cord, no apoptotic signs were found. These results suggest that at the early stage of mnd disease, ER stress is responsible for a precocious dysfunction/degeneration in selective CNS structures of mnd mice (cerebellum, hippocampus and retina); whereas a TNF-dependent inflammation might take place in the cerebral cortex and spinal cord. The ER stress-induced UPR activation is structure specific as a CHOP-dependent pathway mediates the cerebellar and hippocampal degeneration and a caspase-12-dependent pathway is involved in the retinal degeneration. Finally, NF-kB appears to be a key element in that it may provide both adaptive or survival responses. (literal)
Prodotto di
Autore CNR
Insieme di parole chiave

Incoming links:


Autore CNR di
Prodotto
Insieme di parole chiave di
data.CNR.it