4.6 Article

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

Journal

Publisher

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2021.05.016

Keywords

Neurodegeneration; Autophagy; Ageing; Parkin

Funding

  1. Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2013/08028-1, 2018/07592-4]
  2. FAPESP [2018/11946-6]
  3. Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES) [001]
  4. Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)

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Autophagy is a pathway crucial for various cellular functions and has been linked to the pathology of neurodegenerative diseases. Alterations in expression of autophagy-related proteins may play a role in the development of Alzheimer's disease.
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. (c) 2021 Elsevier Inc. All rights reserved.

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