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

Molecules

Irina Milisav²  Duᘚn Šuput²  Samo Ribarič²  Michael Berger¹ 

[1] Institute of Pathophysiology, Faculty of Medicine, Zaloška 4, Ljubljana SI-1000, SloveniaInstitute of Pathophysiology, Faculty of Medicine, Zaloška 4, Ljubljana SI-1000, Slovenia;

关键词: Alzheimer’s disease;    autophagy;    neurodegeneration;    Parkinson’s disease;    prion diseases;    proteostasis;    unfolded protein response;   

DOI  :  10.3390/molecules201219865

来源: mdpi

【 摘 要 】

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.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.