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• W3183580556 abstract "In Alzheimer's disease (AD), amyloid-β (Aβ) generation and upstream β-secretase 1 (BACE1) expression appear to be driven by oxidative stress via c-Jun N-terminal kinase (JNK), p38, and Interferon-Induced, Double-Stranded RNA-Activated Protein Kinase (PKR). In addition, inflammatory molecules, including lipopolysaccharide (LPS), induce genes central to Aβ genesis, such as BACE1, via nuclear factor-κB (NFκB). However, additional triggers of Aβ generation remain poorly understood and might represent novel opportunities for therapeutic intervention. Based on mechanistic studies and elevated ectopic oxidatively damaged DNA (oxoDNA) levels in preclinical AD, mild cognitive impairment, and AD patients, we hypothesize oxoDNA contributes to β-amyloidosis starting from the earliest stages of AD through multiple pathways. OxoDNA induces mitogen-activated protein kinase kinase kinase kinase 4 (MAP4K4), thereby sensitizing the brain to oxidative stress-induced JNK activation and BACE1 transcription. It also induces myeloid differentiation primary response 88 (MyD88) and activates protein kinase CK2, thereby increasing NFκB activation and BACE1 induction. OxoDNA increases oxidative stress via nuclear factor erythroid 2-related factor 2 (Nrf2) ectopic localization, likely augmenting JNK-mediated BACE1 induction. OxoDNA likely also promotes β-amyloidosis via absent in melanoma 2 (AIM2) induction. Falsifiable predictions of this hypothesis include that deoxyribonuclease treatment should decrease Aβ and possibly slow cognitive decline in AD patients. While formal testing of this hypothesis remains to be performed, a case report has found deoxyribonuclease I treatment improved a severely demented AD patient's Mini-Mental Status Exam score from 3 to 18 at 2 months. There is preliminary preclinical and clinical evidence suggesting that ectopic oxidatively damaged DNA may act as an inflammatory damage-associated molecular pattern contributing to Aβ generation in AD, and deoxyribonuclease I should be formally evaluated to test whether it can decrease Aβ levels and slow cognitive decline in AD patients." @default.
• W3183580556 created "2021-08-02" @default.
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• W3183580556 date "2021-07-20" @default.
• W3183580556 modified "2023-09-26" @default.
• W3183580556 title "Does oxidatively damaged DNA drive amyloid-β generation in Alzheimer’s disease? A hypothesis" @default.
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• W3183580556 cites W1975803474 @default.
• W3183580556 cites W1979046857 @default.
• W3183580556 cites W1983730442 @default.
• W3183580556 cites W1988991201 @default.
• W3183580556 cites W1994704865 @default.
• W3183580556 cites W1999854171 @default.
• W3183580556 cites W2001320403 @default.
• W3183580556 cites W2001665323 @default.
• W3183580556 cites W2007279797 @default.
• W3183580556 cites W2009141757 @default.
• W3183580556 cites W2020567039 @default.
• W3183580556 cites W2032315452 @default.
• W3183580556 cites W2041402562 @default.
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• W3183580556 cites W2049901166 @default.
• W3183580556 cites W2050630633 @default.
• W3183580556 cites W2054223500 @default.
• W3183580556 cites W2056044698 @default.
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• W3183580556 cites W2062084653 @default.
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• W3183580556 cites W2082890018 @default.
• W3183580556 cites W2088177247 @default.
• W3183580556 cites W2088835723 @default.
• W3183580556 cites W2097778464 @default.
• W3183580556 cites W2107983069 @default.
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• W3183580556 cites W2158215064 @default.
• W3183580556 cites W2158738222 @default.
• W3183580556 cites W2165427528 @default.
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• W3183580556 doi "https://doi.org/10.1080/01677063.2021.1954641" @default.
• W3183580556 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/34282704" @default.
• W3183580556 hasPublicationYear "2021" @default.
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