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The DOI matches its Crossref record; 10 of the 10 references it cites were found in a registry or an index.

Presenilin Is Necessary for Efficient Proteolysis through the Autophagy–Lysosome System in a γ-Secretase-Independent Manner

Neely, Kara M., Green, Kim N., LaFerla, Frank M.·2011·The Journal of Neuroscience
DOI 10.1523/jneurosci.5156-10.2010PMC PMC3064964
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Abstract

Presenilins are ubiquitous, intramembrane proteins that function in Alzheimer's disease (AD) as the catalytic component of the γ-secretase complex. Familial AD mutations in presenilin are known to exacerbate lysosomal pathology. Hence, we sought to elucidate the function endogenous, wild-type presenilins play in autophagy-mediated protein degradation. We report the finding that genetic deletion or knockdown of presenilins alters many autophagy-related proteins demonstrating a buildup of autophagosomes, indicative of dysfunction in the system. Presenilin-deficient cells inefficiently clear long-lived proteins and fail to build up autophagosomes when challenged with lysosomal inhibitors. Our studies further show that γ-secretase inhibitors do not adversely impact autophagy, indicating that the role of presenilins in autophagy is independent of γ-secretase activity. Based on our findings, we conclude that endogenous, wild-type presenilins are necessary for proper protein degradation through the autophagosome–lysosome system by functioning at the lysosomal level. The role of presenilins in autophagy has many implications for its function in neurological diseases such as AD.

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  • Presenilin function is disrupted in patients with familial AD mutations in PS.

    “Presenilin (PS) function, which is disrupted in patients with familial AD mutations in PS, is associated with dysfunctional lysosomal proteolysis and autophagy (Lee et al., 2010;Lie et al., 2022;Neely et al., 2011;Reddy et al., 2016)”

    From Hippocampal TMEM55B overexpression in the 5XFAD mouse model of Alzheimer's disease (2024) · cites this paper as Neely et al., 2011

  • Presenilin function is associated with dysfunctional lysosomal proteolysis and autophagy.

    “Presenilin (PS) function, which is disrupted in patients with familial AD mutations in PS, is associated with dysfunctional lysosomal proteolysis and autophagy (Lee et al., 2010;Lie et al., 2022;Neely et al., 2011;Reddy et al., 2016)”

    From Hippocampal TMEM55B overexpression in the 5XFAD mouse model of Alzheimer's disease (2024) · cites this paper as Neely et al., 2011

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Research works printed but not linked: 58

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Metadata

Authors
Neely, K. M., Green, K. N., & LaFerla, F. M.
Venue
The Journal of Neuroscience
Publisher
Society for Neuroscience
Published
2011-02-23
Volume
31
Issue
8
Pages
2781-2791
ISSN
  • 0270-6474
  • 1529-2401
DOI
10.1523/jneurosci.5156-10.2010
PMC
PMC3064964
Cited by
134
References
10
Language
en
Licence
creativecommons.org/licenses/by-nc-sa/4.0/ (vor, 181 d)

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