The fine-tuning of proteolytic pathways in Alzheimer's disease.
Several integrated proteolytic systems contribute to the maintenance of cellular homeostasis through the continuous removal of misfolded, aggregated or oxidized proteins and damaged organelles. Among these systems, the proteasome and autophagy play the major role in protein quality control, which is a fundamental issue in non-proliferative cells such as neurons. Disturbances in the functionality of these two pathways are frequently observed in neurodegenerative diseases, like Alzheimer's disease, and reflect the accumulation of protease-resistant, deleterious protein aggregates. In this review, we explored the sophisticated crosstalk between the ubiquitin-proteasome system and autophagy in the removal of the harmful structures that characterize Alzheimer's disease neurons. We also dissected the role of the numerous shuttle factors and chaperones that, directly or indirectly interacting with ubiquitin and LC3, are used for cargo selection and delivery to one pathway or the other.
Department of Biosciences and Veterinary Medicine, School of Biosciences and Veterinary Medicine, University of Camerino, Via Gentile III da Varano, 62032, Camerino, Italy. valentina.cecarini@unicam.it.
Valentina
V
Cecarini
Department of Biosciences and Veterinary Medicine, School of Biosciences and Veterinary Medicine, University of Camerino, Via Gentile III da Varano, 62032, Camerino, Italy.
Laura
L
Bonfili
Department of Biosciences and Veterinary Medicine, School of Biosciences and Veterinary Medicine, University of Camerino, Via Gentile III da Varano, 62032, Camerino, Italy.
Massimiliano
M
Cuccioloni
Department of Biosciences and Veterinary Medicine, School of Biosciences and Veterinary Medicine, University of Camerino, Via Gentile III da Varano, 62032, Camerino, Italy.
Matteo
M
Mozzicafreddo
Department of Biosciences and Veterinary Medicine, School of Biosciences and Veterinary Medicine, University of Camerino, Via Gentile III da Varano, 62032, Camerino, Italy.
Mauro
M
Angeletti
Pennington Biomedical Research Centre, Louisiana State University System, Baton Rouge, LA, 70808, USA.
Jeffrey N
JN
Keller
Department of Biosciences and Veterinary Medicine, School of Biosciences and Veterinary Medicine, University of Camerino, Via Gentile III da Varano, 62032, Camerino, Italy.
Anna Maria
AM
Eleuteri
D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology*; D001343:Autophagy; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D018832:Molecular Chaperones / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D059748:Proteolysis; D025801:Ubiquitin / Q000378:metabolism*
C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins; D018832:Molecular Chaperones; D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex
Alzheimer’s disease; Autophagy; Chaperone; Proteasome; Ubiquitin