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- W2554377152 endingPage "175909141667907" @default.
- W2554377152 startingPage "175909141667907" @default.
- W2554377152 abstract "Sensory neuropathies are the most common neurological complication of HIV. Of these, distal sensory polyneuropathy (DSP) is directly caused by HIV infection and characterized by length-dependent axonal degeneration of dorsal root ganglion (DRG) neurons. Mechanisms for axonal degeneration in DSP remain unclear, but recent experiments revealed that the HIV glycoprotein gp120 is internalized and localized within axons of DRG neurons. Based on these findings, we investigated whether intra-axonal gp120 might impair fast axonal transport (FAT), a cellular process critical for appropriate maintenance of the axonal compartment. Significantly, we found that gp120 severely impaired both anterograde and retrograde FAT. Providing a mechanistic basis for these effects, pharmacological experiments revealed an involvement of various phosphotransferases in this toxic effect, including members of mitogen-activated protein kinase pathways (Tak-1, p38, and c-Jun N-terminal Kinase (JNK)), inhibitor of kappa-B-kinase 2 (IKK2), and PP1. Biochemical experiments and axonal outgrowth assays in cell lines and primary cultures extended these findings. Impairments in neurite outgrowth in DRG neurons by gp120 were rescued using a Tak-1 inhibitor, implicating a Tak-1 mitogen-activated protein kinase pathway in gp120 neurotoxicity. Taken together, these observations indicate that kinase-based impairments in FAT represent a novel mechanism underlying gp120 neurotoxicity consistent with the dying-back degeneration seen in DSP. Targeting gp120-based impairments in FAT with specific kinase inhibitors might provide a novel therapeutic strategy to prevent axonal degeneration in DSP." @default.
- W2554377152 created "2016-11-30" @default.
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- W2554377152 date "2016-11-20" @default.
- W2554377152 modified "2023-09-23" @default.
- W2554377152 title "HIV Glycoprotein Gp120 Impairs Fast Axonal Transport by Activating Tak1 Signaling Pathways" @default.
- W2554377152 cites W1133715286 @default.
- W2554377152 cites W1661652663 @default.
- W2554377152 cites W1772259437 @default.
- W2554377152 cites W1849091229 @default.
- W2554377152 cites W1965957039 @default.
- W2554377152 cites W1969554594 @default.
- W2554377152 cites W1970182993 @default.
- W2554377152 cites W1972591971 @default.
- W2554377152 cites W1978853862 @default.
- W2554377152 cites W1978999158 @default.
- W2554377152 cites W1984979116 @default.
- W2554377152 cites W1993182734 @default.
- W2554377152 cites W1993762028 @default.
- W2554377152 cites W1994367893 @default.
- W2554377152 cites W1996016174 @default.
- W2554377152 cites W2003239995 @default.
- W2554377152 cites W2011884125 @default.
- W2554377152 cites W2013690402 @default.
- W2554377152 cites W2016437687 @default.
- W2554377152 cites W2021258666 @default.
- W2554377152 cites W2022978872 @default.
- W2554377152 cites W2027433436 @default.
- W2554377152 cites W2028309086 @default.
- W2554377152 cites W2029663297 @default.
- W2554377152 cites W2029847351 @default.
- W2554377152 cites W2032856835 @default.
- W2554377152 cites W2033210129 @default.
- W2554377152 cites W2037472543 @default.
- W2554377152 cites W2047126558 @default.
- W2554377152 cites W2047514293 @default.
- W2554377152 cites W2048320127 @default.
- W2554377152 cites W2052970339 @default.
- W2554377152 cites W2057803128 @default.
- W2554377152 cites W2059421466 @default.
- W2554377152 cites W2064802719 @default.
- W2554377152 cites W2065697951 @default.
- W2554377152 cites W2067550112 @default.
- W2554377152 cites W2071998530 @default.
- W2554377152 cites W2077977333 @default.
- W2554377152 cites W2083019341 @default.
- W2554377152 cites W2085052329 @default.
- W2554377152 cites W2085574958 @default.
- W2554377152 cites W2086914876 @default.
- W2554377152 cites W2089405771 @default.
- W2554377152 cites W2089692447 @default.
- W2554377152 cites W2089720517 @default.
- W2554377152 cites W2091035365 @default.
- W2554377152 cites W2092018624 @default.
- W2554377152 cites W2092312715 @default.
- W2554377152 cites W2092729353 @default.
- W2554377152 cites W2093530590 @default.
- W2554377152 cites W2099795189 @default.
- W2554377152 cites W2103119746 @default.
- W2554377152 cites W2106179404 @default.
- W2554377152 cites W2117769423 @default.
- W2554377152 cites W2126522816 @default.
- W2554377152 cites W2129971794 @default.
- W2554377152 cites W2131180540 @default.
- W2554377152 cites W2133183625 @default.
- W2554377152 cites W2135349758 @default.
- W2554377152 cites W2136145428 @default.
- W2554377152 cites W2139155915 @default.
- W2554377152 cites W2141372231 @default.
- W2554377152 cites W2144301785 @default.
- W2554377152 cites W2144414931 @default.
- W2554377152 cites W2146504279 @default.
- W2554377152 cites W2147151936 @default.
- W2554377152 cites W2147943204 @default.
- W2554377152 cites W2149949545 @default.
- W2554377152 cites W2157076525 @default.
- W2554377152 cites W2159713664 @default.
- W2554377152 cites W2161782628 @default.
- W2554377152 cites W2163289722 @default.
- W2554377152 cites W2314229549 @default.
- W2554377152 cites W2322242712 @default.
- W2554377152 cites W2322798515 @default.
- W2554377152 cites W2407129904 @default.
- W2554377152 cites W2413760602 @default.
- W2554377152 cites W2790805946 @default.
- W2554377152 cites W3022626577 @default.
- W2554377152 doi "https://doi.org/10.1177/1759091416679073" @default.
- W2554377152 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5119683" @default.
- W2554377152 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/27872270" @default.
- W2554377152 hasPublicationYear "2016" @default.
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