Related Experiment Video

Updated: May 12, 2026

Profiling Ubiquitin and Ubiquitin-like Dependent Post-translational Modifications and Identification of Significant Alterations
10:26

Profiling Ubiquitin and Ubiquitin-like Dependent Post-translational Modifications and Identification of Significant Alterations

Published on: November 7, 2019

The modifier matrix: emerging roles of ubiquitin-like proteins in Alzheimer's disease

Tingxiang Yan1, Justine Vaquer1, Wolfdieter Springer1,2

  • 1Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224 USA.

Molecular Neurodegeneration Advances
|May 11, 2026
PubMed

Ubiquitin and ubiquitin-like proteins (UBLs) have emerged as critical regulators of protein homeostasis and cellular signaling, processes that are increasingly recognized as central to the pathogenesis of Alzheimer's disease (AD). This review explores the expanding roles of UBL modifiers, including SUMO, NEDD8, ISG15, UFM1, and ATG8/ATG12, in the development and progression of AD. We discuss how these post-translational modifications influence key pathological features of AD such as amyloid-beta accumulation and neurofibrillary tangles formation, as well as their impact on neuronal function, proteostasis, and neuroinflammation. Recent advances in our understanding of the enzymatic machinery mediating these modifications, and the interplay between different UBL proteins, offer new insights into the molecular mechanisms underlying AD. Furthermore, we highlight emerging therapeutic strategies targeting UBL pathways, which may provide novel avenues for intervention in AD. By integrating current findings, this review underscores the significance of UBL proteins in AD and identifies future directions for research aimed at unraveling their complex roles in neurodegeneration.

Keywords:
ATG12ATG8Alzheimer’s diseaseAmyloid-betaISG15MAPTNEDD8SUMOTauUFM1UbiquitinUbiquitin-like proteins

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