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The Nonfibrillar Amyloid β‐Peptide Induces Apoptotic Neuronal Cell Death
Author(s) -
Pillot Thierry,
Drouet Béatrice,
Queillé Sophie,
Labeur Christine,
Vandekerckhove Joël,
Rosseneu Maryvonne,
PinçonRaymond Martine,
Chambaz Jean
Publication year - 1999
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1999.0731626.x
Subject(s) - peptide , neurodegeneration , neurotoxicity , programmed cell death , dna fragmentation , apoptosis , fragmentation (computing) , amyloid beta , biochemistry , biology , microbiology and biotechnology , chemistry , biophysics , medicine , toxicity , ecology , disease , organic chemistry
: The toxicity of the nonaggregated amyloid β‐peptide (1‐40) [Aβ(1‐40)] on the viability of rat cortical neurons in primary culture was investigated. We demonstrated that low concentrations of Aβ peptide, in a nonfibrillar form, induced a time‐ and dose‐dependent apoptotic cell death, including DNA condensation and fragmentation. We compared the neurotoxicity of the Aβ(1‐40) peptide with those of several Aβ‐peptide domains, comprising the membrane‐destabilizing C‐terminal domain of Aβ peptide (e.g., amino acids 29‐40 and 29‐42). These peptides reporduced the effects of the (1‐40) peptide, whereas mutant nonfusogenic Aβ peptides and the central region of the Aβ peptide (e.g., amino acids 13‐28) had no effect on cell viability. We further demonstrated that the neurotoxicity of the nonaggregated Aβ peptide paralleled a rapid and stable interaction between the Aβ peptide and the plasma membrane of neurons, preceding apoptosis and DNa fragmentation. By contrast, the peptide in a fibrillar form induced a rapid and dramatic neuronal death mainly through a necrotic pathway, under our conditions. Taken together, our results suggest that Aβ induces neuronal cell death by either apoptosis and necrosis and that an interaction between the nonfibrillar C‐terminal domain of the Aβ peptide and the plasma membrane of cortical neurons might represent an early event in a cascade leading to neurodegeneration.