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- W2022943683 abstract "Apolipoprotein (apo) E4, a 299-aa protein and a major risk factor for Alzheimer's disease, can be cleaved to generate C-terminal-truncated fragments that cause neurotoxicity in vitro and neurodegeneration and behavioral deficits in transgenic mice. To investigate this neurotoxicity, we expressed apoE4 with C- or N-terminal truncations or mutations in transfected Neuro-2a cells. ApoE4 (1-272) was neurotoxic, but full-length apoE4(1-299) and apoE4(1-240) were not, suggesting that the lipid-binding region (amino acids 241-272) mediates the neurotoxicity and that amino acids 273-299 are protective. A quadruple mutation in the lipid-binding region (I250A, F257A, W264R, and V269A) abolished the neurotoxicity of apoE4(1-272), and single mutations in the region of amino acids 273-299 (L279Q, K282A, or Q284A) made full-length apoE4 neurotoxic. Immunofluorescence staining showed that apoE4(1-272) formed filamentous inclusions containing phosphorylated tau in some cells and interacted with mitochondria in others, leading to mitochondrial dysfunction as determined by MitoTracker staining and flow cytometry. ApoE4(241-272) did not cause mitochondrial dysfunction or neurotoxicity, suggesting that the lipid-binding region alone is insufficient for neurotoxicity. Truncation of N-terminal sequences (amino acids 1-170) containing the receptor-binding region (amino acids 135-150) and triple mutations within that region (R142A, K146A, and R147A) abolished the mitochondrial interaction and neurotoxicity of apoE4(1-272). Further analysis showed that the receptor-binding region is required for escape from the secretory pathway and that the lipid-binding region mediates mitochondrial interaction. Thus, the lipid- and receptor-binding regions in apoE4 fragments act together to cause mitochondrial dysfunction and neurotoxicity, which may be important in Alzheimer's disease pathogenesis." @default.
- W2022943683 created "2016-06-24" @default.
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- W2022943683 date "2005-12-12" @default.
- W2022943683 modified "2023-10-18" @default.
- W2022943683 title "Lipid- and receptor-binding regions of apolipoprotein E4 fragments act in concert to cause mitochondrial dysfunction and neurotoxicity" @default.
- W2022943683 cites W1492557229 @default.
- W2022943683 cites W1498746132 @default.
- W2022943683 cites W1513849159 @default.
- W2022943683 cites W1546031868 @default.
- W2022943683 cites W1555517932 @default.
- W2022943683 cites W1616350046 @default.
- W2022943683 cites W1896684749 @default.
- W2022943683 cites W1958661641 @default.
- W2022943683 cites W1964203272 @default.
- W2022943683 cites W1965136528 @default.
- W2022943683 cites W1965643342 @default.
- W2022943683 cites W1974825648 @default.
- W2022943683 cites W1978813419 @default.
- W2022943683 cites W1980362319 @default.
- W2022943683 cites W1981224477 @default.
- W2022943683 cites W1983994226 @default.
- W2022943683 cites W1984737558 @default.
- W2022943683 cites W1985859760 @default.
- W2022943683 cites W1986144956 @default.
- W2022943683 cites W1993121285 @default.
- W2022943683 cites W2001582257 @default.
- W2022943683 cites W2006409771 @default.
- W2022943683 cites W2008412361 @default.
- W2022943683 cites W2010390315 @default.
- W2022943683 cites W2019351427 @default.
- W2022943683 cites W2021181758 @default.
- W2022943683 cites W2021333248 @default.
- W2022943683 cites W2034945178 @default.
- W2022943683 cites W2034968148 @default.
- W2022943683 cites W2036362108 @default.
- W2022943683 cites W2041192235 @default.
- W2022943683 cites W2043090568 @default.
- W2022943683 cites W2045147739 @default.
- W2022943683 cites W2048351474 @default.
- W2022943683 cites W2052243021 @default.
- W2022943683 cites W2052288531 @default.
- W2022943683 cites W2056822801 @default.
- W2022943683 cites W2056851090 @default.
- W2022943683 cites W2058799638 @default.
- W2022943683 cites W2063505049 @default.
- W2022943683 cites W2074111274 @default.
- W2022943683 cites W2076859770 @default.
- W2022943683 cites W2079335891 @default.
- W2022943683 cites W2081122171 @default.
- W2022943683 cites W2094914629 @default.
- W2022943683 cites W2097039472 @default.
- W2022943683 cites W2099290024 @default.
- W2022943683 cites W2100295360 @default.
- W2022943683 cites W2105668301 @default.
- W2022943683 cites W2105803743 @default.
- W2022943683 cites W2106067304 @default.
- W2022943683 cites W2109200274 @default.
- W2022943683 cites W2112222544 @default.
- W2022943683 cites W2119556701 @default.
- W2022943683 cites W2121101037 @default.
- W2022943683 cites W2128565374 @default.
- W2022943683 cites W2152192643 @default.
- W2022943683 cites W2156998090 @default.
- W2022943683 cites W2159367229 @default.
- W2022943683 cites W2159538597 @default.
- W2022943683 cites W2162846333 @default.
- W2022943683 cites W2163915292 @default.
- W2022943683 cites W2164303459 @default.
- W2022943683 cites W2165427528 @default.
- W2022943683 cites W2169096667 @default.
- W2022943683 cites W2170218376 @default.
- W2022943683 cites W2171960085 @default.
- W2022943683 cites W2315335674 @default.
- W2022943683 cites W2346906895 @default.
- W2022943683 cites W4210821588 @default.
- W2022943683 cites W4234896620 @default.
- W2022943683 cites W4291712481 @default.
- W2022943683 cites W4295202935 @default.
- W2022943683 cites W98152484 @default.
- W2022943683 doi "https://doi.org/10.1073/pnas.0508254102" @default.
- W2022943683 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/1311737" @default.
- W2022943683 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/16344479" @default.
- W2022943683 hasPublicationYear "2005" @default.
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