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P1–076: Formation and neurotoxicity of high‐mass beta‐amyloid assemblies, amylospheroids, from amyloid precursor proteins in neurons with Alzheimer's mutations
Author(s) -
Komura Hitomi,
Muramatsu Shinichi,
Hoshi Minako
Publication year - 2013
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.2013.05.297
Subject(s) - neurotoxicity , amyloid (mycology) , hippocampal formation , chemistry , amyloid precursor protein , golgi apparatus , microbiology and biotechnology , neurodegeneration , microglia , brefeldin a , immunostaining , amyloid beta , biology , neuroscience , alzheimer's disease , biochemistry , pathology , immunohistochemistry , immunology , endoplasmic reticulum , peptide , toxicity , medicine , disease , inflammation , organic chemistry , inorganic chemistry
data and revealed that (1) Ab overload induces neuronal apoptosis mainly through a mitochondrial-mediated apoptotic pathway; (2) that several genes important for axon guidance are misregulated in Tg2576mice, and thus may be responsible for synaptic degeneration; and (3) that TF and TF-binding motifs disturbances might participate in the inflammatory process. Conclusions: Numerous studies have identified that Ab plays a significant role in the onset and progression of AD. One mechanism by which Ab can induce apoptosis and impair synaptic connections is through the disturbance of mitochondrial function, leading to dysregulation in Ca 2+ homeostasis and reactive oxygen species production. Understanding the downstream mechanisms of the mitochondrial-mediated apoptotic pathwaymay uncover potential therapeutic targets for AD. The findings of this study also suggest that transcription is a significant functional group in the analysis of gene expression profiles.Modulators of inflammatory processes and neuronal Ca 2+ signaling, which were impaired by some disturbances TF and TF-binding motifs, may be potential therapeutic targets for AD.