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PrP and β‐Amyloid Fragments Activate Different Neurotoxic Mechanisms in Cultured Mouse Cells
Author(s) -
Brown David R.,
Herms Jochen W.,
Schmidt Bernhard,
Kretzschmar Hans A.
Publication year - 1997
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.1997.tb01470.x
Subject(s) - toxicity , apoptosis , programmed cell death , microbiology and biotechnology , amyloid (mycology) , biology , receptor , neurodegeneration , neurotoxicity , chemistry , neuroscience , biochemistry , disease , pathology , medicine , botany , organic chemistry
Alzheimer's disease and prion diseases such as Creutzfeldt‐Jakob disease are caused by as yet undefined metabolic disturbances of normal cellular proteins, the amyloid precursor protein and the prion protein (PrP). Synthetic fragments of both proteins, β‐amyloid 25–35 (βA25–35) and PrP106–126, have been shown to be toxic to neurons in culture. Cell death in both cases occurs by apoptosis. Here we show that there are considerable differences in the mechanisms involved. Thus, PrP106–126 is not toxic to cortical cell cultures of PrP knockout mouse neurons whereas PA25–35 is. The toxicity of both peptides involves Ca 2+ uptake through voltage‐sensitive Ca 2+ channels but only PrP106–126 toxicity involves the activity of NMDA receptors. The toxicity of PA25–35, but not PrP106–126, is attenuated by the action of forskolin. These results indicate that PrP106–126 and βA25–35 induce neuronal apoptosis through different mechanisms.