Pro-NGF isolated from the human brain affected by Alzheimer's disease induces neuronal apoptosis mediated by p75NTR.
The pro-form of nerve growth factor (pro-NGF) has been shown to be a high affinity ligand for p75NTR and to induce apoptosis through this receptor. It has been reported that pro-NGF, rather than mature NGF, is the predominant form of this neurotrophin in human brain. In the present work we studied the potential involvement of pro-NGF purified from human brains affected by Alzheimer's disease (AD), where it is especially abundant, in the neuronal apoptosis observed in this disease. Western blot analysis of human brain tissue showed the existence of several pro-NGF forms. Some of these pro-NGF forms were significantly increased in AD brain cortex in a disease stage-dependent manner. Pro-NGF, purified by chromatography from human AD brains, induced apoptotic cell death in sympathetic neurons and in a p75NTR stably transfected cell line. Blocking p75NTR in cell culture abolished neuronal apoptosis caused by pro-NGF. p75NTR-transfected cells underwent apoptosis in the presence of pro-NGF while control wild-type cells did not. Taken together, these results indicate that pro-NGF purified from AD human brains can induce apoptosis in neuronal cell cultures through its interaction with the p75NTR receptor.
Pedraza
Carlos E
CE
Laboratori de Neuropatología Molecular, Departament de Ciències Mèdiques Bàsiques, Universitat de Lleida, C/ Montserrat Roig 2, 25008 Lleida, Spain.
Podlesniy
Petar
P
Vidal
Noemí
N
Arévalo
Juan Carlos
JC
Lee
Ramee
R
Hempstead
Barbara
B
Ferrer
Isidre
I
Iglesias
Montse
M
Espinet
Carme
C
D016475:3T3 Cells; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D002845:Chromatography; D003720:Densitometry; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008875:Middle Aged; D020932:Nerve Growth Factor / Q000096:biosynthesis* / Q000502:physiology*; D009414:Nerve Growth Factors / Q000378:metabolism; D009474:Neurons / Q000473:pathology*; D016716:PC12 Cells; D011498:Protein Precursors / Q000096:biosynthesis* / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection; D014357:Trypsin / Q000494:pharmacology
D009414:Nerve Growth Factors; D011498:Protein Precursors; D020800:Receptor, Nerve Growth Factor; D017475:Receptors, Nerve Growth Factor; C061397:pro-nerve growth factor, human; D020932:Nerve Growth Factor; D014357:Trypsin