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- W2898246389 abstract "OMI/HTRA2 (high-temperature requirement serine protease A2) is a mitochondrial serine protease involved in several cellular processes, including autophagy, chaperone activity, and apoptosis. Few studies on the role of OMI/HTRA2 in Alzheimer's disease (AD) are available, but none on its relationship with the cholinergic system and neurotrophic factors as well as other AD-related proteins. In this study, immunohistochemical analyses revealed that AD patients had a higher cytosolic distribution of OMI/HTRA2 protein compared to controls. Quantitative analyses on brain extracts indicated a significant increase in the active form of OMI/HTRA2 in the AD brain. Activated OMI/HTRA2 protein positively correlated with stress-associated read-through acetylcholinesterase activity. In addition, α7 nicotinic acetylcholine receptor gene expression, a receptor also known to be localized on the outer membrane of mitochondria, showed a strong correlation with OMI/HTRA2 gene expression in three different brain regions. Interestingly, the activated OMI/HTRA2 levels also correlated with the activity of the acetylcholine-biosynthesizing enzyme, choline acetyltransferase (ChAT); with levels of the neurotrophic factors, NGF and BDNF; with levels of the soluble fragments of amyloid precursor protein (APP); and with gene expression of the microtubule-associated protein tau in the examined brain regions. Overall, the results demonstrate increased levels of the mitochondrial serine protease OMI/HTRA2, and a coherent pattern of association between the activated form of OMI/HTRA2 and several key proteins involved in AD pathology. In this paper, we propose a new hypothetical model to highlight the importance and needs of further investigation on the role of OMI/HTRA2 in the mitochondrial function and AD." @default.
- W2898246389 created "2018-11-02" @default.
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- W2898246389 date "2018-10-25" @default.
- W2898246389 modified "2023-10-12" @default.
- W2898246389 title "Increased Active OMI/HTRA2 Serine Protease Displays a Positive Correlation with Cholinergic Alterations in the Alzheimer’s Disease Brain" @default.
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- W2898246389 doi "https://doi.org/10.1007/s12035-018-1383-3" @default.
- W2898246389 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6657433" @default.
- W2898246389 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30361890" @default.
- W2898246389 hasPublicationYear "2018" @default.
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