Matches in SemOpenAlex for { <https://semopenalex.org/work/W2896867712> ?p ?o ?g. }
Showing items 1 to 80 of
80
with 100 items per page.
- W2896867712 abstract "A failure in protein homeostasis is a common factor in the most prevalent age-related neurodegenerative diseases associated with protein aggregation. The protein, ubiquilin-2 (UBQLN2), helps ensure protein homeostasis by shuttling ubiquitinated substrates to the proteasome for degradation and by modulating autophagy. UBQLN2 is implicated indirectly in various dementing disorders, including tauopathies and synucleinopathies, due to its accumulation in neuropathological deposits. More recently, UBQLN2 has been directly connected as a cause of frontotemporal dementia when mutated, and our laboratory has linked the toxicity of UBQLN2 to its aggregation. To evaluate whether UBQLN2 regulates tau and α-synuclein expression, aggregation or clearance, we co-expressed tau or α-synuclein with UBQLN2 in human embryonic kidney-293 cells and assessed levels of monomeric and oligomeric tau or α-synuclein. The specificity of UBQLN2 in lowering levels of tau and α-synuclein was compared to that of UBQLN1, a highly homologous protein that lacks a robust correlation to disease. The ability of these two ubiquilins to regulate other common aggregate-prone disease proteins, including TDP43 and Huntingtin, was also evaluated. To determine whether changes to UBQLN2 occur in the disease setting, brain tissue from human disease, as well as from mice overexpressing tau and α-synuclein, was analyzed for UBQLN2 levels. Co-expressed UBQLN2 markedly lowered levels of monomeric α-synuclein and both monomeric and oligomeric tau. Conversely, siRNA knockdown of UBQLN2 significantly elevated levels of α-synuclein and tau monomer and oligomers. In contrast, UBQLN1 did not exhibit the same ability to decrease tau and α-synuclein levels. Likewise, UBQLN2 selectively had an effect on levels of TDP43 and Huntingtin. The possibility that UBQLN2 also undergoes alterations in disease was evidenced by the fact that more UBQLN2 was insoluble in human disease brain and in transgenic mouse models of synucleinopathy and tauopathy than in healthy/non-transgenic controls. Our findings highlight a new role for UBQLN2—but not UBQLN1—in managing levels of tau and α-synuclein and other important neurodegenerative disease proteins. However, lowered levels of soluble UBQLN2 in disease brain suggest that UBQLN2 may be dysfunctional in synucleinopathies and tauopathies, due to its intrinsic aggregation or accumulation in disease aggregates." @default.
- W2896867712 created "2018-10-26" @default.
- W2896867712 creator A5015942281 @default.
- W2896867712 creator A5055180300 @default.
- W2896867712 creator A5072009686 @default.
- W2896867712 creator A5088484515 @default.
- W2896867712 date "2018-07-01" @default.
- W2896867712 modified "2023-10-16" @default.
- W2896867712 title "P3‐188: UBIQUILIN‐2 REGULATION OF TAU AND α‐SYNUCLEIN IN NEURODEGENERATIVE DISEASE" @default.
- W2896867712 doi "https://doi.org/10.1016/j.jalz.2018.06.1546" @default.
- W2896867712 hasPublicationYear "2018" @default.
- W2896867712 type Work @default.
- W2896867712 sameAs 2896867712 @default.
- W2896867712 citedByCount "0" @default.
- W2896867712 crossrefType "journal-article" @default.
- W2896867712 hasAuthorship W2896867712A5015942281 @default.
- W2896867712 hasAuthorship W2896867712A5055180300 @default.
- W2896867712 hasAuthorship W2896867712A5072009686 @default.
- W2896867712 hasAuthorship W2896867712A5088484515 @default.
- W2896867712 hasBestOaLocation W28968677122 @default.
- W2896867712 hasConcept C136238340 @default.
- W2896867712 hasConcept C142724271 @default.
- W2896867712 hasConcept C169760540 @default.
- W2896867712 hasConcept C190283241 @default.
- W2896867712 hasConcept C203522944 @default.
- W2896867712 hasConcept C27740335 @default.
- W2896867712 hasConcept C2776477761 @default.
- W2896867712 hasConcept C2776925932 @default.
- W2896867712 hasConcept C2777440831 @default.
- W2896867712 hasConcept C2778641062 @default.
- W2896867712 hasConcept C2779134260 @default.
- W2896867712 hasConcept C2779483572 @default.
- W2896867712 hasConcept C2779734285 @default.
- W2896867712 hasConcept C2781172350 @default.
- W2896867712 hasConcept C2781449126 @default.
- W2896867712 hasConcept C54355233 @default.
- W2896867712 hasConcept C55493867 @default.
- W2896867712 hasConcept C71924100 @default.
- W2896867712 hasConcept C86803240 @default.
- W2896867712 hasConcept C95444343 @default.
- W2896867712 hasConceptScore W2896867712C136238340 @default.
- W2896867712 hasConceptScore W2896867712C142724271 @default.
- W2896867712 hasConceptScore W2896867712C169760540 @default.
- W2896867712 hasConceptScore W2896867712C190283241 @default.
- W2896867712 hasConceptScore W2896867712C203522944 @default.
- W2896867712 hasConceptScore W2896867712C27740335 @default.
- W2896867712 hasConceptScore W2896867712C2776477761 @default.
- W2896867712 hasConceptScore W2896867712C2776925932 @default.
- W2896867712 hasConceptScore W2896867712C2777440831 @default.
- W2896867712 hasConceptScore W2896867712C2778641062 @default.
- W2896867712 hasConceptScore W2896867712C2779134260 @default.
- W2896867712 hasConceptScore W2896867712C2779483572 @default.
- W2896867712 hasConceptScore W2896867712C2779734285 @default.
- W2896867712 hasConceptScore W2896867712C2781172350 @default.
- W2896867712 hasConceptScore W2896867712C2781449126 @default.
- W2896867712 hasConceptScore W2896867712C54355233 @default.
- W2896867712 hasConceptScore W2896867712C55493867 @default.
- W2896867712 hasConceptScore W2896867712C71924100 @default.
- W2896867712 hasConceptScore W2896867712C86803240 @default.
- W2896867712 hasConceptScore W2896867712C95444343 @default.
- W2896867712 hasIssue "7S_Part_21" @default.
- W2896867712 hasLocation W28968677121 @default.
- W2896867712 hasLocation W28968677122 @default.
- W2896867712 hasOpenAccess W2896867712 @default.
- W2896867712 hasPrimaryLocation W28968677121 @default.
- W2896867712 hasRelatedWork W1779994739 @default.
- W2896867712 hasRelatedWork W1969342645 @default.
- W2896867712 hasRelatedWork W2047691740 @default.
- W2896867712 hasRelatedWork W2050987407 @default.
- W2896867712 hasRelatedWork W2084665273 @default.
- W2896867712 hasRelatedWork W2299132392 @default.
- W2896867712 hasRelatedWork W2570634615 @default.
- W2896867712 hasRelatedWork W2800805986 @default.
- W2896867712 hasRelatedWork W3139476025 @default.
- W2896867712 hasRelatedWork W4214907302 @default.
- W2896867712 hasVolume "14" @default.
- W2896867712 isParatext "false" @default.
- W2896867712 isRetracted "false" @default.
- W2896867712 magId "2896867712" @default.
- W2896867712 workType "article" @default.