Matches in SemOpenAlex for { <https://semopenalex.org/work/W2608367614> ?p ?o ?g. }
- W2608367614 endingPage "20" @default.
- W2608367614 startingPage "1" @default.
- W2608367614 abstract "When optineurin mutations showed up on the amyotrophic lateral sclerosis (ALS) landscape in 2010, they differed from most other ALS-causing genes. They seemed to act by loss- rather than gain-of-function, and it was unclear how a polyubiquitin-binding adaptor protein, which was proposed to regulate a variety of cellular functions including cell signaling and vesicle trafficking, could mediate neuroprotection. This review discusses the considerable progress that has been made since then. A large number of mutations in optineurin and optineurin-interacting proteins TANK-binding kinase (TBK1) and p62/SQSTM-1 have been found in the ALS patients, suggesting a common neuroprotective pathway. Moreover, functional studies of the ALS-causing optineurin mutations and the recently established optineurin ubiquitin-binding deficient and knockout mouse models helped identify three major mechanisms likely to mediate neuroprotection: regulation of autophagy, mitigation of (chronic) inflammatory signaling, and blockade of necroptosis. These three processes crosstalk, and require multiple levels of control, many of which can be mediated by optineurin. Based on the role of optineurin in multiple processes and the unexpected finding that targeted optineurin deletion in microglia and oligodendrocytes ultimately leads to the same phenotype of axonal degeneration despite different initial defects, we propose that the failure of the weakest link in the optineurin neuroprotective network is sufficient to disturb homeostasis and set-off the domino effect that could ultimately lead to neurodegeneration." @default.
- W2608367614 created "2017-05-05" @default.
- W2608367614 creator A5013908886 @default.
- W2608367614 creator A5016353227 @default.
- W2608367614 creator A5020540455 @default.
- W2608367614 creator A5039981622 @default.
- W2608367614 creator A5050613626 @default.
- W2608367614 creator A5080431922 @default.
- W2608367614 date "2017-07-01" @default.
- W2608367614 modified "2023-09-30" @default.
- W2608367614 title "Optineurin in amyotrophic lateral sclerosis: Multifunctional adaptor protein at the crossroads of different neuroprotective mechanisms" @default.
- W2608367614 cites W1098620786 @default.
- W2608367614 cites W1483162601 @default.
- W2608367614 cites W1497027037 @default.
- W2608367614 cites W1528922106 @default.
- W2608367614 cites W1542273561 @default.
- W2608367614 cites W1565351177 @default.
- W2608367614 cites W1576514072 @default.
- W2608367614 cites W1619082318 @default.
- W2608367614 cites W1621668151 @default.
- W2608367614 cites W1639349134 @default.
- W2608367614 cites W1709160233 @default.
- W2608367614 cites W1710904042 @default.
- W2608367614 cites W1752988765 @default.
- W2608367614 cites W1767107461 @default.
- W2608367614 cites W1865484534 @default.
- W2608367614 cites W1919353 @default.
- W2608367614 cites W1923330562 @default.
- W2608367614 cites W1926674024 @default.
- W2608367614 cites W1949280308 @default.
- W2608367614 cites W1964442232 @default.
- W2608367614 cites W1967106374 @default.
- W2608367614 cites W1967709357 @default.
- W2608367614 cites W1968444524 @default.
- W2608367614 cites W1974504862 @default.
- W2608367614 cites W1974987657 @default.
- W2608367614 cites W1976765363 @default.
- W2608367614 cites W1977348907 @default.
- W2608367614 cites W1980918455 @default.
- W2608367614 cites W1981329326 @default.
- W2608367614 cites W1983560493 @default.
- W2608367614 cites W1984861969 @default.
- W2608367614 cites W1985484942 @default.
- W2608367614 cites W1986278788 @default.
- W2608367614 cites W1986978728 @default.
- W2608367614 cites W1992532731 @default.
- W2608367614 cites W1993064034 @default.
- W2608367614 cites W1993813911 @default.
- W2608367614 cites W1994925296 @default.
- W2608367614 cites W1995042437 @default.
- W2608367614 cites W1995744610 @default.
- W2608367614 cites W1995747121 @default.
- W2608367614 cites W1996381116 @default.
- W2608367614 cites W1998645760 @default.
- W2608367614 cites W1999732669 @default.
- W2608367614 cites W2000984052 @default.
- W2608367614 cites W2003618511 @default.
- W2608367614 cites W2004492484 @default.
- W2608367614 cites W2005757378 @default.
- W2608367614 cites W2005928129 @default.
- W2608367614 cites W2006406228 @default.
- W2608367614 cites W2008176593 @default.
- W2608367614 cites W2009225398 @default.
- W2608367614 cites W2013504579 @default.
- W2608367614 cites W2018636808 @default.
- W2608367614 cites W2019706623 @default.
- W2608367614 cites W2019986404 @default.
- W2608367614 cites W2020893142 @default.
- W2608367614 cites W2021168188 @default.
- W2608367614 cites W2022812113 @default.
- W2608367614 cites W2023122823 @default.
- W2608367614 cites W2023384214 @default.
- W2608367614 cites W2025413109 @default.
- W2608367614 cites W2028478497 @default.
- W2608367614 cites W2029303246 @default.
- W2608367614 cites W2029582543 @default.
- W2608367614 cites W2030194678 @default.
- W2608367614 cites W2030280505 @default.
- W2608367614 cites W2031964319 @default.
- W2608367614 cites W2032195857 @default.
- W2608367614 cites W2032700869 @default.
- W2608367614 cites W2032996510 @default.
- W2608367614 cites W2033158384 @default.
- W2608367614 cites W2033283555 @default.
- W2608367614 cites W2033344638 @default.
- W2608367614 cites W2033562377 @default.
- W2608367614 cites W2034254855 @default.
- W2608367614 cites W2038096193 @default.
- W2608367614 cites W2040239818 @default.
- W2608367614 cites W2040678584 @default.
- W2608367614 cites W2043291430 @default.
- W2608367614 cites W2044638164 @default.
- W2608367614 cites W2045991166 @default.
- W2608367614 cites W2046864536 @default.
- W2608367614 cites W2047365750 @default.
- W2608367614 cites W2048308372 @default.
- W2608367614 cites W2048813950 @default.
- W2608367614 cites W2051362437 @default.