Abstract:
:Aggregated tau is a hallmark neuropathological feature in numerous neurodegenerative disorders. Previous studies aiming to validate aggregated tau pathology as a pathogenic driver of neurodegeneration in correlation to characteristic behavioral phenotypes have had shortcomings. Although studies on soluble tau pathology have effectively addressed these shortcomings, the role of soluble tau in the molecular pathogenesis of neurodegeneration is not yet unequivocally established. In sporadic Alzheimer's disease (AD), the relevance of soluble tau pathology in endolysosomal dysfunction and autophagic stress, some of the earliest disease manifestations, is unclear. In this study, we report that soluble 4R0N tau overexpression affects the expression levels of certain markers associated with the endolysosomal system and autophagy. Moreover, through live-cell imaging, we found that the vesicular dynamics of early endosomes were affected with respect to spatiotemporal parameters and vesicle maturation. Additionally, we observed the localization of amyloid precursor protein (APP) along the endocytic pathway and found that upon overexpression of soluble 4R0N tau, APP was preferentially localized to the endocytic compartments implicated in the amyloidogenic pathway. Overall, our observations indicate that soluble 4R0N tau abrogates the dynamics of the endolysosomal system, autophagy, and affects the trafficking of APP. Since the amyloidogenic processing of APP occurs during its progression through the endocytic pathway, our results suggest that the generation of amyloid-β (Aβ) might also be modulated.
journal_name
Front Aging Neuroscijournal_title
Frontiers in aging neuroscienceauthors
Mahendran TS,Suresh SN,Garimella L,Manjithaya Rdoi
10.3389/fnagi.2020.537712subject
Has Abstractpub_date
2020-11-05 00:00:00pages
537712issn
1663-4365journal_volume
12pub_type
杂志文章abstract::It is assumed that DNA sequences are conserved in the diverse cell types present in a multicellular organism like the human being. Thus, in order to compare the sequences in the genome of DNA from different individuals, nucleic acid is commonly isolated from a single tissue. In this regard, blood cells are widely used...
journal_title:Frontiers in aging neuroscience
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journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
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journal_title:Frontiers in aging neuroscience
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journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
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abstract::Aberrations in brain microcirculation and the associated increase in blood-brain-barrier (BBB) permeability in addition to neuroinflammation and Aβ deposition observed in Alzheimer's disease (AD) and ischemia have gained considerable attention recently. However, the role of microvascular homeostasis as a pathogenic su...
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doi:10.3389/fnagi.2016.00259
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journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2020.00010
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abstract::Dietary folic acid deficiency induced early hearing loss in C57BL/6J mice after 2-months, corroborates the epidemiological association previously described between vitamin deficiency and this sensory impairment. However, this strain is prone to early hearing loss, and hence we decided to analyze whether the effects ex...
journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2016.00209
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pub_type: 杂志文章
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journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2016.00252
更新日期:2016-10-25 00:00:00
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journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2019.00326
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journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2016.00094
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journal_title:Frontiers in aging neuroscience
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journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2014.00335
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journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
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journal_title:Frontiers in aging neuroscience
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journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2012.00036
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journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章,评审
doi:10.3389/fnagi.2017.00207
更新日期:2017-06-23 00:00:00
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journal_title:Frontiers in aging neuroscience
pub_type: 杂志文章
doi:10.3389/fnagi.2017.00188
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