The Role of Unfolded Protein Response and Mitogen-Activated Protein Kinase Signaling in Neurodegenerative Diseases with Special Focus on Prion Diseases

Frontiers in Aging Neuroscience
Syed Zahid Ali ShahLifeng Yang

Abstract

Prion diseases are neurodegenerative pathologies characterized by the accumulation of a protease-resistant form of the cellular prion protein named prion protein scrapie (PrP(Sc)) in the brain. PrP(Sc) accumulation in the endoplasmic reticulum (ER) result in a dysregulated calcium (Ca(2+)) homeostasis and subsequent initiation of unfolded protein response (UPR) leading to neuronal dysfunction and apoptosis. The molecular mechanisms for the transition between adaptation to ER stress and ER stress-induced apoptosis are still unclear. Mitogen-activated protein kinases (MAPKs) are serine/threonine protein kinases that rule the signaling of many extracellular stimuli from plasma membrane to the nucleus. However the identification of numerous points of cross talk between the UPR and MAPK signaling pathways may contribute to our understanding of the consequences of ER stress in prion diseases. Indeed the MAPK signaling network is known to regulate cell cycle progression and cell survival or death responses following a variety of stresses including misfolded protein response stress. In this article, we review the UPR signaling in prion diseases and discuss the triad of MAPK signaling pathways. We also describe the role played by MAPK s...Continue Reading

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Dec 5, 2019·International Journal of Molecular Sciences·Rodrigo Portes UreshinoGustavo José da Silva Pereira
Jun 19, 2018·Molecular Neurobiology·S VelaMaría J Ramirez
May 31, 2018·Molecular Medicine Reports·Hong-Wei WangFeng Gao
Mar 9, 2019·International Journal of Molecular Sciences·Syed Zahid Ali ShahLifeng Yang
Feb 8, 2020·Current Neuropharmacology·Shareen Singh, Thakur Gurjeet Singh
Jul 3, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Yeon Joo ChoiSoo Young Choi
Aug 17, 2021·Oxidative Medicine and Cellular Longevity·Ji-Hong MoonSang-Youel Park
Mar 16, 2019·ACS Infectious Diseases·Takeshi FuchigamiMorio Nakayama

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Methods Mentioned

BETA
protein folding
GTPases
ubiquitination
transfection

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