PERK Pathway and Neurodegenerative Disease: To Inhibit or to Activate?

Talya ShachamGerardo Z Lederkremer


With the extension of life span in recent decades, there is an increasing burden of late-onset neurodegenerative diseases, for which effective treatments are lacking. Neurodegenerative diseases include the widespread Alzheimer's disease (AD) and Parkinson's disease (PD), the less frequent Huntington's disease (HD) and Amyotrophic Lateral Sclerosis (ALS) and also rare early-onset diseases linked to mutations that cause protein aggregation or loss of function in genes that maintain protein homeostasis. The difficulties in applying gene therapy approaches to tackle these diseases is drawing increasing attention to strategies that aim to inhibit cellular toxicity and restore homeostasis by intervening in cellular pathways. These include the unfolded protein response (UPR), activated in response to endoplasmic reticulum (ER) stress, a cellular affliction that is shared by these diseases. Special focus is turned to the PKR-like ER kinase (PERK) pathway of the UPR as a target for intervention. However, the complexity of the pathway and its ability to promote cell survival or death, depending on ER stress resolution, has led to some confusion in conflicting studies. Both inhibition and activation of the PERK pathway have been reported ...Continue Reading


Aug 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·A ReinerA B Young
Nov 1, 1985·Journal of Neuropathology and Experimental Neurology·J P VonsattelE P Richardson
Nov 25, 2000·Human Molecular Genetics·F TrettelM E MacDonald
Jun 19, 2001·The Journal of Biological Chemistry·E HeissC Gerhäuser
Jun 4, 2002·Nature Reviews. Molecular Cell Biology·Randal J KaufmanStacey M Arnold
Oct 16, 2003·Molecular and Cellular Biology·Ann-Hwee LeeLaurie H Glimcher
Jul 28, 2004·Proceedings of the National Academy of Sciences of the United States of America·Krishna M Vattem, Ronald C Wek
Dec 14, 2004·Cell Death and Differentiation·H KadowakiH Ichijo
Feb 16, 2005·Annual Review of Physiology·Dietmar Kültz
Jun 24, 2005·Acta Neuropathologica·J J M HoozemansW Scheper
Jan 7, 2006·Cell Death and Differentiation·D LindholmL Korhonen
Jul 11, 2006·Science·Julie Hollien, Jonathan S Weissman
Jan 26, 2007·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Anna-Leena SokkaLaura Korhonen
Jan 27, 2007·Biochemical and Biophysical Research Communications·J J M HoozemansW Scheper
Jul 6, 2007·Neuropharmacology·Richard L KrausJohn J Renger
Feb 7, 2008·Chemical Research in Toxicology·Girish RachakondaMichael L Freeman
May 16, 2008·Human & Experimental Toxicology·Mark P Mattson
Nov 19, 2008·Genes & Development·Martin L Duennwald, Susan Lindquist
Feb 3, 2009·Molecular Neurobiology·Kohsuke KanekuraMasaaki Matsuoka
May 13, 2009·The Journal of Biological Chemistry·Alisia CarnemollaFrancesca Persichetti
Dec 29, 2009·Journal of Neuroinflammation·Antero SalminenJohanna Ojala

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Jun 30, 2021·Experimental Neurology·Subramaniam JayanthiJean Lud Cadet

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