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Induction of amyloid precursor protein by the neurotoxic peptide, amyloid‐beta 25–35, causes retinal ganglion cell death
Author(s) -
Tsuruma Kazuhiro,
Tanaka Yuka,
Shimazawa Masamitsu,
Hara Hideaki
Publication year - 2010
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 - 10.1111/j.1471-4159.2010.06724.x
Subject(s) - retinal ganglion cell , programmed cell death , intracellular , amyloid precursor protein , retinal , amyloid (mycology) , p3 peptide , amyloid beta , bace1 as , retina , neurotoxicity , microbiology and biotechnology , biology , ganglion , biochemistry of alzheimer's disease , alzheimer's disease , peptide , chemistry , medicine , neuroscience , pathology , biochemistry , toxicity , disease , apoptosis
J. Neurochem. (2010) 113 , 1545–1564. Abstract Patients with Alzheimer’s disease (AD) show a significantly increased incidence of glaucoma. AD is also associated with the occurrence of the neurotoxic peptide amyloid beta (Aβ). Therefore, we investigated whether Aβ is associated with retinal cell death in a retinal ganglion cell line (RGC‐5). Treatment with Aβ 25–35 , a neurotoxic fragment of Aβ, induced cell death in RGC‐5 in both a concentration‐ and time‐dependent manner. The amount of amyloid precursor protein was increased by treatment of RGC‐5 and primary culture of mouse cortical neurons with fibril Aβ 25–35 and Aβ 1–42 , which is a putative physiological neurotoxic fragment of Aβ present in AD. Amyloid precursor protein knockdown inhibited the cell death induced by Aβ 25–35 . Treatment with Aβ 25–35 increased the amount of intracellular Aβ 1–40 and Aβ 1–42 , while β‐ and γ‐secretase inhibitors reduced cell death. Thus, the regulation of Aβ can be viewed as a new therapeutic target for glaucoma, especially in patients with coincident AD.