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Abstract #26462 Published in IGR 12-3
Induction of amyloid precursor protein by the neurotoxic peptide, amyloid-beta 25-35, causes retinal ganglion cell death
Tsuruma K; Tanaka Y; Shimazawa M; Hara HJournal of Neurochemistry 2010; 113: 1545-1554
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 (A(beta)). Therefore, we investigated whether A(beta) is associated with retinal cell death in a retinal ganglion cell line (RGC-5). Treatment with A(beta)(25-35), a neurotoxic fragment of A(beta), 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 A(beta)(25-35) and A(beta)(1-42), which is a putative physiological neurotoxic fragment of A(beta) present in AD. Amyloid precursor protein knockdown inhibited the cell death induced by A(beta)(25-35). Treatment with A(beta)(25-35) increased the amount of intracellular A(beta)(1-40) and A(beta)(1-42), while (beta)- and (gamma)-secretase inhibitors reduced cell death. Thus, the regulation of A(beta) can be viewed as a new therapeutic target for glaucoma, especially in patients with coincident AD.
H. Hara. Department of Biofunctional Evaluation, Molecular Pharmacology, Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196, Japan. hidehara@gifu-pu.ac.jp
Classification:
2.13 Retina and retinal nerve fibre layer (Part of: 2 Anatomical structures in glaucoma)
11.8 Neuroprotection (Part of: 11 Medical treatment)
3.6 Cellular biology (Part of: 3 Laboratory methods)
