Phosphorylated c-MYC expression in Alzheimer disease, Pick's disease, progressive supranuclear palsy and corticobasal degeneration

TY - JOUR

T1 - Phosphorylated c-MYC expression in Alzheimer disease, Pick's disease, progressive supranuclear palsy and corticobasal degeneration

AU - Ferrer, I

AU - Blanco, R

AU - Carmona, M

AU - Puig, B

AU - Puig Martorell, Berta

PY - 2001/10/1

Y1 - 2001/10/1

N2 - 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.

AB - 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.

KW - Aged

KW - Aged, 80 and over

KW - Alzheimer Disease

KW - Apoptosis

KW - Brain Diseases

KW - Caspase 3

KW - Caspases

KW - Female

KW - Humans

KW - Immunohistochemistry

KW - Male

KW - Mitogen-Activated Protein Kinases

KW - Neurofibrillary Tangles

KW - Phosphorylation

KW - Pick Disease of the Brain

KW - Proto-Oncogene Proteins c-myc

KW - Supranuclear Palsy, Progressive

KW - tau Proteins

M3 - SCORING: Journal article

C2 - 11679086

VL - 27

SP - 343

EP - 351

JO - NEUROPATH APPL NEURO

JF - NEUROPATH APPL NEURO

SN - 0305-1846

IS - 5

ER -