Axonally synthesized ATF4 transmits a neurodegenerative signal across brain regions

Jimena BaleriolaUlrich Hengst


In Alzheimer's disease (AD) brain, exposure of axons to Aβ causes pathogenic changes that spread retrogradely by unknown mechanisms, affecting the entire neuron. We found that locally applied Aβ1-42 initiates axonal synthesis of a defined set of proteins including the transcription factor ATF4. Inhibition of local translation and retrograde transport or knockdown of axonal Atf4 mRNA abolished Aβ-induced ATF4 transcriptional activity and cell loss. Aβ1-42 injection into the dentate gyrus (DG) of mice caused loss of forebrain neurons whose axons project to the DG. Protein synthesis and Atf4 mRNA were upregulated in these axons, and coinjection of Atf4 siRNA into the DG reduced the effects of Aβ1-42 in the forebrain. ATF4 protein and transcripts were found with greater frequency in axons in the brain of AD patients. These results reveal an active role for intra-axonal translation in neurodegeneration and identify ATF4 as a mediator for the spread of AD pathology.


Jan 15, 1982·Biochemical and Biophysical Research Communications·S M PenningrothC W Bardin
Jan 1, 1993·European Neurology·H BraakJ Bohl
Oct 28, 1997·Stroke; a Journal of Cerebral Circulation·W I Rosenblum
Nov 25, 2003·The Journal of Biological Chemistry·Julien AverousPierre Fafournoux
Aug 12, 2005·Nature Methods·Anne M TaylorNoo Li Jeon
Oct 26, 2005·Biochemical Society Transactions·R C WekT G Anthony
May 26, 2006·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Ulrich HengstSamie R Jaffrey
Jun 14, 2006·Proceedings of the National Academy of Sciences of the United States of America·Daniela C DieterichErin M Schuman
Jan 5, 2007·Lab on a Chip·Michael W Toepke, David J Beebe
May 1, 2007·The International Journal of Biochemistry & Cell Biology·Kurosh Ameri, Adrian L Harris
May 10, 2007·Nature Protocols·Jeong Won ParkNoo Li Jeon
Jan 15, 2008·Nature Cell Biology·Llewellyn J CoxSamie R Jaffrey
Feb 3, 2009·Acta Neuropathologica·Khalid IqbalInge Grundke-Iqbal
May 22, 2009·Lab on a Chip·Salil P DesaiJoel Voldman
Aug 21, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Caroline DubacqAlain Trembleau
May 4, 2010·Trends in Neurosciences·Eran PerlsonErika L F Holzbaur
Oct 15, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Bhupinder P S VohraJeffrey Milbrandt
Oct 14, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Dianna E WillisJeffery L Twiss
Feb 22, 2012·Cell·Byung C YoonChristine E Holt
Dec 5, 2012·Cold Spring Harbor Perspectives in Biology·David Ron, Heather P Harding
Jul 31, 2013·Developmental Neurobiology·Sheng-Jian Ji, Samie R Jaffrey
Aug 21, 2013·PLoS Computational Biology·Michael LawrenceVincent J Carey
Apr 1, 2014·Cell·Hosung JungChristine E Holt
Dec 18, 2014·Genome Biology·Michael I LoveSimon Anders

❮ Previous
Next ❯


Mar 13, 2016·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·Andreia Filipa Rodrigues Batista, Ulrich Hengst
Oct 9, 2015·Developmental Neurobiology·Juan Pablo LezanaMiguel Bronfman
Aug 12, 2015·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Xuling LiAshley I Bush
Nov 10, 2014·Molecular Neurobiology·Na WeiDan Liu
Jun 14, 2015·Neurobiology of Aging·Miki HayakawaToshiyuki Nakagawa
Jun 16, 2015·Frontiers in Cellular Neuroscience·Sergio T FerreiraFernanda G De Felice
Jun 5, 2015·Frontiers in Aging Neuroscience·Fernanda G De Felice, Mychael V Lourenco
Apr 11, 2015·Progress in Neurobiology·Mychael V LourencoFernanda G De Felice
Nov 6, 2014·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Jimena Baleriola, Ulrich Hengst
Dec 11, 2014·Acta Neuropathologica·Rebecca M NisbetJürgen Götz
May 2, 2016·Current Opinion in Neurobiology·Paul G Donlin-AspWilfried Rossoll
Jun 21, 2016·Cell·Toshiaki ShigeokaChristine E Holt
Aug 30, 2016·Journal of Pharmacological Sciences·Toru HosoiKoichiro Ozawa
Apr 28, 2016·The Journal of Comparative Neurology·Li-Qing JinMichael E Selzer
Oct 19, 2016·Cytoskeleton·Hermano Martins Bellato, Glaucia Noeli Maroso Hajj
Feb 22, 2017·Traffic·Víctor Hugo CornejoAndrés Couve
Jun 9, 2017·The Neuroscientist : a Review Journal Bringing Neurobiology, Neurology and Psychiatry·Amar N KarJeffery L Twiss
Dec 22, 2016·Nature Communications·Joseph M VillarinUlrich Hengst
Dec 20, 2015·Molecular & Cellular Proteomics : MCP·Solène DebaisieuxGiampietro Schiavo
Aug 25, 2015·Molecular & Cellular Proteomics : MCP·Atsushi Saito, Valeria Cavalli
Jun 21, 2017·Biochimica Et Biophysica Acta. General Subjects·Ashley Chin, Eric Lécuyer
Jul 22, 2017·Nature Reviews. Neurology·Claudio Hetz, Smita Saxena
Dec 1, 2017·Nucleic Acids Research·Jun YuSheng-Jian Ji
Mar 25, 2018·BMC Neuroscience·Ruping FanNadejda L Korneeva
Nov 18, 2017·The FEBS Journal·Yannis Gerakis, Claudio Hetz
Sep 6, 2017·Journal of Cell Science·Cynthia GomesJeffery L Twiss
Jan 13, 2018·Frontiers in Cellular Neuroscience·Priyamvada M PitaleMarina Gorbatyuk
Dec 13, 2017·Frontiers in Immunology·Yuan YangBoxu Ren
Apr 1, 2015·Molecular and Cellular Biology·Francesca MorettiOlivier Pertz
Jul 25, 2018·Molecular & Cellular Proteomics : MCP·Seung Joon LeeJeffery L Twiss
Feb 20, 2019·Otolaryngology--head and Neck Surgery : Official Journal of American Academy of Otolaryngology-Head and Neck Surgery·Michael B MontalbanoMichael J Pitman
Jun 15, 2019·International Journal of Molecular Sciences·Toshiyuki Nakagawa, Kazunori Ohta
Aug 1, 2019·Brain : a Journal of Neurology·Jordi Creus-MuncunillEsther Pérez-Navarro

❮ Previous
Next ❯

Related Concepts

Related Feeds

ApoE Phenotypes

Apolipoprotein E (APOE) is a protein involved in fat metabolism and associated with the pathogenesis of Alzheimer's disease and cardiovascular disease. Here is the latest research on APOE phenotypes.

Basal Forebrain & Food Avoidance

Neurons in the basal forebrain play specific roles in regulating feeding. Here are the latest discoveries pertaining to the basal forebrain and food avoidance.

Alzheimer's Disease: APP

Amyloid precursor protein (APP) proteolysis is critical for the development of Alzheimer's disease, a neurodegenerative disease associated with accumulation of amyloid plaques in the brain. Here is the latest research on APP and Alzheimer's disease.

Antisense Oligonucleotides: ND

This feed focuses on antisense oligonucleotide therapies such as Inotersen, Nusinursen, and Patisiran, in neurodegenerative diseases including amyotrophic lateral sclerosis.

Alzheimer's Disease: Transcription

Impaired transcription is associated with the pathogenesis and progression of conditions such as Alzheimer's disease (AD). Here are the latest discoveries pertaining to transcription and AD.

Basal Forebrain- Circuits

Basal forebrain is a region in the brain important for production of acetylcholine and is the major cholinergic output of the CNS. Discover the latest research on circuits in the basal forebrain here.

Alzheimer's Disease: Amyloid Beta

Alzheimer's disease is a neurodegenerative disease associated with the accumulation of amyloid plaques in the brain; these plaques are comprised of amyloid beta deposits. Here is the latest research in this field.

Alzheimer's Disease: RNA Sequencing

RNA sequencing studies have shed light on the genetic and molecular mechanisms related to the pathophysiology of Alzheimer's disease (AD). This feed follows papers using RNA sequencing technologies in Alzheimer's research.

Alzheimer's Disease: APOE

Apolipoprotein E (APOE) polymorphic alleles are major genetic risk factors for Alzheimer's disease. Discover the latest research on APOE and other genetic determinants of Alzheimer's disease here.

Alzheimer's Disease: Endosomes

Dysfunctional endosomal trafficking may be associated with Alzheimer’s disease (AD) pathology. Targeting the endosome may advance treatment options for AD. Here is the latest research on endosomes and AD.

Cell eTOC

Cell is a scientific journal publishing research across a broad range of disciplines within the life sciences field. Discover the latest research from Cell here.

Bioinformatics in Biomedicine

Bioinformatics in biomedicine incorporates computer science, biology, chemistry, medicine, mathematics and statistics. Discover the latest research on bioinformatics in biomedicine here.

Related Papers

Journal of Visualized Experiments : JoVE
Joseph HarrisNoo Li Jeon
Movement Disorders : Official Journal of the Movement Disorder Society
Isabelle Beaulieu-Boire, Susan H Fox
© 2021 Meta ULC. All rights reserved