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Unfolded Protein Response and Macroautophagy in Alzheimer’s, Parkinson’s and Prion Diseases

by Irina Milisav 1,2,†, Dušan Šuput 1,† and Samo Ribarič 1,*,†
1
Institute of Pathophysiology, Faculty of Medicine, Zaloška 4, Ljubljana SI-1000, Slovenia
2
Faculty of Health Sciences, Zdravstvena pot 5, SI-1000 Ljubljana, Slovenija
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editors: Michael Berger and Jean Jacques Vanden Eynde
Molecules 2015, 20(12), 22718-22756; https://doi.org/10.3390/molecules201219865
Received: 30 October 2015 / Revised: 30 November 2015 / Accepted: 9 December 2015 / Published: 18 December 2015
Proteostasis are integrated biological pathways within cells that control synthesis, folding, trafficking and degradation of proteins. The absence of cell division makes brain proteostasis susceptible to age-related changes and neurodegeneration. Two key processes involved in sustaining normal brain proteostasis are the unfolded protein response and autophagy. Alzheimer’s disease (AD), Parkinson’s disease (PD) and prion diseases (PrDs) have different clinical manifestations of neurodegeneration, however, all share an accumulation of misfolded pathological proteins associated with perturbations in unfolded protein response and macroautophagy. While both the unfolded protein response and macroautophagy play an important role in the prevention and attenuation of AD and PD progression, only macroautophagy seems to play an important role in the development of PrDs. Macroautophagy and unfolded protein response can be modulated by pharmacological interventions. However, further research is necessary to better understand the regulatory pathways of both processes in health and neurodegeneration to be able to develop new therapeutic interventions. View Full-Text
Keywords: Alzheimer’s disease; autophagy; neurodegeneration; Parkinson’s disease; prion diseases; proteostasis; unfolded protein response Alzheimer’s disease; autophagy; neurodegeneration; Parkinson’s disease; prion diseases; proteostasis; unfolded protein response
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Milisav, I.; Šuput, D.; Ribarič, S. Unfolded Protein Response and Macroautophagy in Alzheimer’s, Parkinson’s and Prion Diseases. Molecules 2015, 20, 22718-22756.

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