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Effects of Lamin A Progeric Mutation (LMNA-Δ50) in Tau Reporter Cell Culture Models

  • Author / Creator
    Han, Zhuang Zhuang
  • Chronological aging is one of the greatest risk factors of tauopathies, yet our understanding about the underlying molecular mechanism is limited. Studying physiological aging often requires an extended timeline and thus presents a significant hurdle for modeling late-onset disorders. In this study, we present an attempt to mimic chronological aging with pathological premature aging. Our approach involves expression of progerin, a truncated form of lamin A found primarily in Hutchinson Gilford progeria syndrome, in established cell culture models for tau protein aggregation. We find that induced aging sensitizes tau inclusion-free cells to tau misfolding events when cells are exposed to pathogenic tau. Significant aggravation of nuclear deformation is observed in cells that are already burdened with tau aggregates. To further investigate progerin-induced cellular changes, mass spectrometry is employed to determine the cellular proteome with and without progerin expression. Our proteomics dataset shows that progerin results in notable but complex alterations in nuclear and endosome-associated proteins, shedding light on their potential involvements in chronological aging.

  • Subjects / Keywords
  • Graduation date
    Fall 2021
  • Type of Item
    Thesis
  • Degree
    Master of Science
  • DOI
    https://doi.org/10.7939/r3-62g9-dy09
  • License
    This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.