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P4‐234: The protection of APP 5‐mer peptide analog 165 on the human neuroblastoma SH‐SY5Y cells damaged by streptozotocin
Author(s) -
Wang Pengwen
Publication year - 2008
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2008.05.2302
Subject(s) - sh sy5y , viability assay , protein kinase b , pi3k/akt/mtor pathway , mtt assay , streptozotocin , chemistry , endocrinology , cell culture , cell growth , medicine , microbiology and biotechnology , biology , cell , apoptosis , neuroblastoma , biochemistry , diabetes mellitus , genetics
are produced from the sequential cleavage of the amyloid precursor protein (APP) carried out by betaand gamma-secretase. Pyramidal neurons of the cerebral cortex and hippocampus appear to be primarily targeted. Abeta peptides, including A 42 and A 40, are found in the blood of both normal and AD individuals. Leakage of these so-called “toxic” peptides into the brain tissue as a result of breakdown in the blood-brain barrier occurs due to age-associated changes in blood vessels, head trauma and stroke. In the brain, these peptides either remain soluble (monomeric or oligomeric) or insoluble (polymeric). Methods: Immunohistochemistry, biological assays. Results: Surprisingly, our results show that Abeta42 is present in and on neurons in the brain and spinal cord in humans throughout life, and is detectable in neurons as early as the fetal stage. It is also detected in the retinal ganglion cells. This widespread presence of Abeta42 in neurons argues against it being toxic to neurons. Furthermore, our results also show that the Abeta42 peptide is able to activate the guanylate cyclase signal transduction pathway in normal brain. Conclusions: Taken together, these results suggest that Abeta42 may be an essential neuronal component, and its abundant presence in the synaptic field of neurons suggest that it may be an essential component of synaptic membranes. However, in the diseased state, an exogenous supply of the peptide, from blood-brain barrier breach, for example, leads to large deposits of Abeta42 within the neurons, displacing the cell’s normal complement of protein synthetic machinery and altering the signal transduction pathways. These actions may be the key to their so-called “toxicity” during Alzheimer’s disease progression.