Cell death signaling in the cerebellum in Creutzfeldt-Jakob disease

TY - JOUR

T1 - Cell death signaling in the cerebellum in Creutzfeldt-Jakob disease

AU - Puig, B

AU - Ferrer, I

AU - Puig Martorell, Berta

PY - 2001/9/1

Y1 - 2001/9/1

N2 - Examination of the expression of proteins linked with signaling pathways commanding cell death and cell survival has been carried out to increase understanding on the mechanisms leading to cell death in the cerebellum in Creutzfeldt-Jakob disease (CJD). Expression of Fas, Fas ligand (Fas-L), ERK, MEK, Bcl-2, Bax, N-myc, c-myc, pro-caspase-2 and active caspase-3 was examined by immunohistochemistry in the cerebellum of six patients with sporadic CJD, three patients with olivopontocerebellar atrophy (OPCA) and six age-matched controls. No modifications in the expression of these proteins were observed in granule cells in CJD and OPCA when compared with controls, except in a few cells in the molecular and granular layers in CJD that displayed dense homogeneous active caspase-3 immunostaining. This suggests selective activation of caspase-3 in association with increased cellular vulnerability in CJD. No modifications in pro-caspase-2 and c-myc immunoreactivity were observed in Purkinje cells in diseased brains when compared with controls. However, increased diffuse Fas, Fas-L, MEK, ERK and Bax expression, and enhanced granular active caspase-3 immunoreactivity was found in the cytoplasm of Purkinje cells in CJD. Increase in Bcl-2 and N-myc occurred in Purkinje cells in CJD and OPCA. These results indicate that enhanced Fas, Fas-L, MERK, ERK, Bax and granular active caspase-3 expression is not lethal to Purkinje cells in CJD, whereas increased Bcl-2 and N-myc does not preclude per se cell death or death survival in CJD and OPCA. These findings point to the likelihood that expression of these cell death proteins in neurodegeneration has functional roles differing from those related with apoptosis.

AB - Examination of the expression of proteins linked with signaling pathways commanding cell death and cell survival has been carried out to increase understanding on the mechanisms leading to cell death in the cerebellum in Creutzfeldt-Jakob disease (CJD). Expression of Fas, Fas ligand (Fas-L), ERK, MEK, Bcl-2, Bax, N-myc, c-myc, pro-caspase-2 and active caspase-3 was examined by immunohistochemistry in the cerebellum of six patients with sporadic CJD, three patients with olivopontocerebellar atrophy (OPCA) and six age-matched controls. No modifications in the expression of these proteins were observed in granule cells in CJD and OPCA when compared with controls, except in a few cells in the molecular and granular layers in CJD that displayed dense homogeneous active caspase-3 immunostaining. This suggests selective activation of caspase-3 in association with increased cellular vulnerability in CJD. No modifications in pro-caspase-2 and c-myc immunoreactivity were observed in Purkinje cells in diseased brains when compared with controls. However, increased diffuse Fas, Fas-L, MEK, ERK and Bax expression, and enhanced granular active caspase-3 immunoreactivity was found in the cytoplasm of Purkinje cells in CJD. Increase in Bcl-2 and N-myc occurred in Purkinje cells in CJD and OPCA. These results indicate that enhanced Fas, Fas-L, MERK, ERK, Bax and granular active caspase-3 expression is not lethal to Purkinje cells in CJD, whereas increased Bcl-2 and N-myc does not preclude per se cell death or death survival in CJD and OPCA. These findings point to the likelihood that expression of these cell death proteins in neurodegeneration has functional roles differing from those related with apoptosis.

KW - Antigens, CD95

KW - Apoptosis

KW - Caspase 2

KW - Caspase 3

KW - Caspases

KW - Cerebellum

KW - Creutzfeldt-Jakob Syndrome

KW - Enzyme Precursors

KW - Fas Ligand Protein

KW - Humans

KW - Immunohistochemistry

KW - Membrane Glycoproteins

KW - Mitogen-Activated Protein Kinase Kinases

KW - Mitogen-Activated Protein Kinases

KW - Olivopontocerebellar Atrophies

KW - Proto-Oncogene Proteins

KW - Proto-Oncogene Proteins c-bcl-2

KW - Proto-Oncogene Proteins c-myc

KW - Signal Transduction

KW - bcl-2-Associated X Protein

M3 - SCORING: Journal article

C2 - 11585244

VL - 102

SP - 207

EP - 215

JO - ACTA NEUROPATHOL

JF - ACTA NEUROPATHOL

SN - 0001-6322

IS - 3

ER -