Parkin is downregulated among autophagy-related proteins prior to hyperphosphorylation of Tau in TS65DN mice

Biochem Biophys Res Commun. 2021 Jul 5:561:59-64. doi: 10.1016/j.bbrc.2021.05.016. Epub 2021 May 18.

Abstract

Autophagy is a pathway through which cells execute a plethora of functions, such as macromolecules and organelles quality control, recycling of building blocks and apoptosis. Numerous studies have shown in the past that autophagy is an important mechanism associated with the pathology of various neurodegenerative diseases, whose impairment may lead to several disease-characteristic phenotypes (e.g. misfolded protein and defective organelles accumulation). With this in mind, we aimed to investigate whether alterations in expression of autophagy-related proteins would show before hyperphosphorylation of Tau, a hallmark of Alzheimer's disease (AD). After analyzing 7 different proteins, we observed that, while Pink1 and p62 show an age-related reduction in the Ts65Dn mice respectively in the locus coeruleus and hippocampus, Parkin shows an age-genotype interaction-associated reduction in both brain areas. This suggests potential outcomes in pathways associated with Parkin that could relate to later stages of the disease development.

Keywords: Ageing; Autophagy; Neurodegeneration; Parkin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology*
  • Animals
  • Autophagy-Related Proteins / metabolism*
  • Disease Models, Animal
  • Down Syndrome / metabolism
  • Down Syndrome / pathology*
  • Down-Regulation
  • Female
  • Male
  • Mice
  • Mice, Transgenic
  • Phosphorylation
  • Ubiquitin-Protein Ligases / metabolism*
  • tau Proteins / metabolism*

Substances

  • Autophagy-Related Proteins
  • tau Proteins
  • Ubiquitin-Protein Ligases
  • parkin protein