Loss of autophagy in the central nervous system causes neurodegeneration in mice

Nature
Masaaki KomatsuKeiji Tanaka

Abstract

Protein quality-control, especially the removal of proteins with aberrant structures, has an important role in maintaining the homeostasis of non-dividing neural cells. In addition to the ubiquitin-proteasome system, emerging evidence points to the importance of autophagy--the bulk protein degradation pathway involved in starvation-induced and constitutive protein turnover--in the protein quality-control process. However, little is known about the precise roles of autophagy in neurons. Here we report that loss of Atg7 (autophagy-related 7), a gene essential for autophagy, leads to neurodegeneration. We found that mice lacking Atg7 specifically in the central nervous system showed behavioural defects, including abnormal limb-clasping reflexes and a reduction in coordinated movement, and died within 28 weeks of birth. Atg7 deficiency caused massive neuronal loss in the cerebral and cerebellar cortices. Notably, polyubiquitinated proteins accumulated in autophagy-deficient neurons as inclusion bodies, which increased in size and number with ageing. There was, however, no obvious alteration in proteasome function. Our results indicate that autophagy is essential for the survival of neural cells, and that impairment of autophagy is ...Continue Reading

Associated Clinical Trials

Dec 2, 2017·Jessica Mandrioli

References

May 9, 2000·The Journal of Biological Chemistry·N TanahashiK Tanaka
Mar 27, 2001·Nature Reviews. Molecular Cell Biology·Y Ohsumi
Mar 5, 2002·Human Molecular Genetics·Carola J M BontekoeBen A Oostra
Apr 5, 2003·Molecular and Cellular Neurosciences·Masato KoikeYasuo Uchiyama
Apr 30, 2003·The Journal of Biological Chemistry·Julie L WebbDavid C Rubinsztein
May 20, 2003·FEBS Letters·Gábor JuhászMiklós Sass
Apr 8, 2004·Developmental Cell·Beth Levine, Daniel J Klionsky
Jul 24, 2004·Nature Medicine·Ella Bossy-WetzelStuart A Lipton
Nov 5, 2004·Nature·Akiko KumaNoboru Mizushima
Nov 6, 2004·Science·Takahiro Shintani, Daniel J Klionsky
Nov 6, 2004·Science·Ichiro NakagawaTamotsu Yoshimori
Dec 14, 2004·Science·Casper PaludanChristian Münz
May 4, 2005·The Journal of Cell Biology·Masaaki KomatsuTomoki Chiba
Jun 28, 2005·Current Opinion in Cell Biology·Fulvio Reggiori, Daniel J Klionsky
Oct 4, 2005·The Journal of Clinical Investigation·Beth Levine, Junying Yuan
Oct 6, 2005·The Journal of Cell Biology·W Haung YuRalph A Nixon

❮ Previous
Next ❯

Citations

Apr 29, 2008·Cellular and Molecular Life Sciences : CMLS·W Li, Y Ye
Nov 8, 2012·Cellular and Molecular Life Sciences : CMLS·Dong WangP Robin Hiesinger
Aug 6, 2011·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Martin GamerdingerChristian Behl
Feb 27, 2009·Basic Research in Cardiology·Roberta A GottliebRobert M Mentzer
Jun 30, 2012·Acta Neuropathologica·Darius Ebrahimi-FakhariPamela J McLean
Aug 7, 2010·Archives of Orthopaedic and Trauma Surgery·Bing WuMing-Hao Zheng
Mar 6, 2008·Histochemistry and Cell Biology·Yasuo UchiyamaMitsuho Sasaki
Jun 21, 2012·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Poonam Sansanwal, Minnie M Sarwal
Jul 10, 2012·Molecules and Cells·Soon-Hee KimTaijoon Chung
May 28, 2013·Molecules and Cells·Stefan W RyterAugustine M K Choi
Nov 9, 2007·Apoptosis : an International Journal on Programmed Cell Death·Andrew Thorburn
Apr 25, 2007·Apoptosis : an International Journal on Programmed Cell Death·Klas BlomgrenLaurent Groc
Jan 28, 2009·Apoptosis : an International Journal on Programmed Cell Death·Avital Eisenberg-Lerner, Adi Kimchi
Jan 24, 2009·Apoptosis : an International Journal on Programmed Cell Death·Oren A LevyLloyd A Greene
Aug 7, 2009·Apoptosis : an International Journal on Programmed Cell Death·Yusuke KusamaKenichi Yoshida
Sep 17, 2009·Apoptosis : an International Journal on Programmed Cell Death·S Steiger-Barraissoul, A Rami
Jan 14, 2010·Apoptosis : an International Journal on Programmed Cell Death·Cristina González-Estévez, Emili Saló
Feb 5, 2010·Apoptosis : an International Journal on Programmed Cell Death·Hansruedi Büeler
Sep 8, 2010·Apoptosis : an International Journal on Programmed Cell Death·Ilan Ziv, Eldad Melamed
Feb 25, 2011·Biogerontology·Maria Markaki, Nektarios Tavernarakis
Apr 5, 2011·Biogerontology·Vanessa M HubbardAna Maria Cuervo
Jan 9, 2009·Journal of Inherited Metabolic Disease·S U Walkley
Apr 30, 2010·Journal of Inherited Metabolic Disease·Cinzia Maria Bellettato, Maurizio Scarpa
Jan 25, 2008·Heart Failure Reviews·Richard N Kitsis, Jagat Narula
Aug 16, 2011·Journal of Neuro-oncology·Jean M Mulcahy Levy, Andrew Thorburn
Aug 31, 2013·Reviews in Endocrine & Metabolic Disorders·Min-Seon KimMyung-Shik Lee
Oct 26, 2013·Reviews in Endocrine & Metabolic Disorders·Sudarshana Purkayastha, Dongsheng Cai
Aug 13, 2009·Current Allergy and Asthma Reports·Akanksha Chaturvedi, Susan K Pierce
Sep 4, 2007·Current Neurology and Neuroscience Reports·Annamaria Ventruti, Ana Maria Cuervo
Apr 29, 2010·Current Neurology and Neuroscience Reports·Arash VelayatiEllen Sidransky
May 28, 2013·Cell Biochemistry and Biophysics·Caroline Park, Ana Maria Cuervo
May 23, 2013·Cell Biochemistry and Biophysics·Javier H JaraP Hande Özdinler
Dec 4, 2010·Immunologic Research·Alexis Dunkle, You-Wen He
Aug 18, 2012·Molecular Neurobiology·Elzbieta JandaVincenzo Mollace
Sep 4, 2012·Molecular Neurobiology·Maria XilouriLeonidas Stefanis
Apr 30, 2013·Molecular Neurobiology·Xi-Chen ZhuLan Tan
Feb 24, 2012·Journal of Biosciences·Ying-Tsen TungYung-Feng Liao
Sep 13, 2012·Neuroscience Bulletin·Feng XuZheng-Hong Qin
Apr 23, 2013·Neurotoxicity Research·Jianbin ZhangJingyuan Chen
Mar 10, 2012·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Paige M DexterGuy A Caldwell
Feb 15, 2013·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Conrad C Weihl
Aug 11, 2007·Brain Research·Nobutoshi MorimotoKoji Abe

❮ Previous
Next ❯

Related Concepts

Related Feeds

Autophagy & Disease

Autophagy is an important cellular process for normal physiology and both elevated and decreased levels of autophagy are associated with disease. Here is the latest research.

Cell Aging

This feed focuses on cellular aging with emphasis on mitochondria, autophagy, and metabolic processes associated with aging and longevity. Here is the latest research on cell aging.

Autophagy & Model Organisms

Autophagy is a cellular process that allows degradation by the lysosome of cytoplasmic components such as proteins or organelles. Here is the latest research on autophagy & model organisms

Cell Aging (Keystone)

This feed focuses on cellular aging with emphasis on the mitochondria, autophagy, and metabolic processes associated with aging and longevity. Here is the latest research on cell aging.

Brain Aging

Here is the latest research on intrinsic and extrinsic factors, as well as pathways and mechanisms that underlie aging in the central nervous system.