Phosphorylated c-MYC expression in Alzheimer disease, Pick's disease, progressive supranuclear palsy and corticobasal degeneration.
Phosphorylated c-Myc (c-Myc-P) expression has been examined by immunohistochemistry, using an antibody that recognizes phosphorylated c-Myc at Thr58 and Ser62, in the brains of Alzheimer disease (AD), Pick's disease (PiD), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD) and age-matched control cases, as well as in human medulloblastomas and central neuroblastomas. Strong c-Myc-P immunoreactivity was seen in dystrophic neurites and neurones with neurofibrillary tangles in AD, and in neurones and glial cells bearing abnormal tau deposits in PiD, PSP and CBD. Previous studies have shown active Ras and increased mitogen-activated protein kinase (MAPK/ERK) expression in neurones and glial cells with abnormal tau deposition in AD and other tauopathies. Since MAPKs phosphorylate c-Myc at Thr58 and Ser62, these observations implicate the Ras/MAP kinase pathway in c-Myc phosphorylation and accumulation in AD and other tauopathies. Previous studies have also shown activation of cell cycle associated proteins in neuronal death. The present results have shown colocalization of nuclear c-Myc-P and active, cleaved caspase-3, a major executioner of apoptosis, in medulloblastomas and central neuroblastomas, thus suggesting phosphorylated c-Myc expression in caspase-3-dependent apoptosis of tumour cells. However, no evidence of caspase-3 activation has been observed in neurones and glial cells with strong phosphorylated c-Myc immunoreactivity in AD, PiD, PSP and CBD. Therefore, it is not clear that the activation of the Ras/MAPK/c-Myc subprogramme leads to neuronal death in AD and other tauopathies.
Ferrer
I
I
Unitat de Neuropatologia, Servei d'Anatomia Patològica, Hospital Princeps d'Espanya, i Departament de Biologia Cellular i Anatomia Patològica, Facultat de Medicina, Universitat de Barcelona, Hospitalet de Llobregat, Spain. iferrer@sakma.es
Blanco
R
R
Carmona
M
M
Puig
B
B
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D017209:Apoptosis; D001927:Brain Diseases / Q000378:metabolism* / Q000473:pathology; D053148:Caspase 3; D020169:Caspases / Q000032:analysis / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016874:Neurofibrillary Tangles / Q000378:metabolism; D010766:Phosphorylation; D020774:Pick Disease of the Brain / Q000378:metabolism / Q000473:pathology; D016271:Proto-Oncogene Proteins c-myc / Q000032:analysis / Q000378:metabolism*; D013494:Supranuclear Palsy, Progressive / Q000378:metabolism / Q000473:pathology; D016875:tau Proteins / Q000378:metabolism
D016271:Proto-Oncogene Proteins c-myc; D016875:tau Proteins; D020928:Mitogen-Activated Protein Kinases; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases