Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice

Taichi Hara, Kenji Nakamura, Makoto Matsui, Akitsugu Yamamoto, Yohko Nakahara, Rika Suzuki-Migishima, Minesuke Yokoyama, Kenji Mishima, Ichiro Saito, Hideyuki Okano, Noboru Mizushima

Research output: Contribution to journalArticle

2407 Citations (Scopus)

Abstract

Autophagy is an intracellular bulk degradation process through which a portion of the cytoplasm is delivered to lysosomes to be degraded. Although the primary role of autophagy in many organisms is in adaptation to starvation, autophagy is also thought to be important for normal turnover of cytoplasmic contents, particularly in quiescent cells such as neurons. Autophagy may have a protective role against the development of a number of neurodegenerative diseases. Here we report that loss of autophagy causes neurodegeneration even in the absence of any disease-associated mutant proteins. Mice deficient for Atg5 (autophagy-related 5) specifically in neural cells develop progressive deficits in motor function that are accompanied by the accumulation of cytoplasmic inclusion bodies in neurons. In Atg5-/- cells, diffuse, abnormal intracellular proteins accumulate, and then form aggregates and inclusions. These results suggest that the continuous clearance of diffuse cytosolic proteins through basal autophagy is important for preventing the accumulation of abnormal proteins, which can disrupt neural function and ultimately lead to neurodegeneration.

Original languageEnglish
Pages (from-to)885-889
Number of pages5
JournalNature
Volume441
Issue number7095
DOIs
Publication statusPublished - 2006 Jun 15
Externally publishedYes

Fingerprint

Autophagy
Neurodegenerative Diseases
Inclusion Bodies
Neurons
Proteins
Mutant Proteins
Starvation
Lysosomes
Cytoplasm

ASJC Scopus subject areas

  • General

Cite this

Hara, T., Nakamura, K., Matsui, M., Yamamoto, A., Nakahara, Y., Suzuki-Migishima, R., ... Mizushima, N. (2006). Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice. Nature, 441(7095), 885-889. https://doi.org/10.1038/nature04724

Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice. / Hara, Taichi; Nakamura, Kenji; Matsui, Makoto; Yamamoto, Akitsugu; Nakahara, Yohko; Suzuki-Migishima, Rika; Yokoyama, Minesuke; Mishima, Kenji; Saito, Ichiro; Okano, Hideyuki; Mizushima, Noboru.

In: Nature, Vol. 441, No. 7095, 15.06.2006, p. 885-889.

Research output: Contribution to journalArticle

Hara, T, Nakamura, K, Matsui, M, Yamamoto, A, Nakahara, Y, Suzuki-Migishima, R, Yokoyama, M, Mishima, K, Saito, I, Okano, H & Mizushima, N 2006, 'Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice', Nature, vol. 441, no. 7095, pp. 885-889. https://doi.org/10.1038/nature04724
Hara T, Nakamura K, Matsui M, Yamamoto A, Nakahara Y, Suzuki-Migishima R et al. Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice. Nature. 2006 Jun 15;441(7095):885-889. https://doi.org/10.1038/nature04724
Hara, Taichi ; Nakamura, Kenji ; Matsui, Makoto ; Yamamoto, Akitsugu ; Nakahara, Yohko ; Suzuki-Migishima, Rika ; Yokoyama, Minesuke ; Mishima, Kenji ; Saito, Ichiro ; Okano, Hideyuki ; Mizushima, Noboru. / Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice. In: Nature. 2006 ; Vol. 441, No. 7095. pp. 885-889.
@article{0a582322ca02469b9f3ceecb11f834cb,
title = "Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice",
abstract = "Autophagy is an intracellular bulk degradation process through which a portion of the cytoplasm is delivered to lysosomes to be degraded. Although the primary role of autophagy in many organisms is in adaptation to starvation, autophagy is also thought to be important for normal turnover of cytoplasmic contents, particularly in quiescent cells such as neurons. Autophagy may have a protective role against the development of a number of neurodegenerative diseases. Here we report that loss of autophagy causes neurodegeneration even in the absence of any disease-associated mutant proteins. Mice deficient for Atg5 (autophagy-related 5) specifically in neural cells develop progressive deficits in motor function that are accompanied by the accumulation of cytoplasmic inclusion bodies in neurons. In Atg5-/- cells, diffuse, abnormal intracellular proteins accumulate, and then form aggregates and inclusions. These results suggest that the continuous clearance of diffuse cytosolic proteins through basal autophagy is important for preventing the accumulation of abnormal proteins, which can disrupt neural function and ultimately lead to neurodegeneration.",
author = "Taichi Hara and Kenji Nakamura and Makoto Matsui and Akitsugu Yamamoto and Yohko Nakahara and Rika Suzuki-Migishima and Minesuke Yokoyama and Kenji Mishima and Ichiro Saito and Hideyuki Okano and Noboru Mizushima",
year = "2006",
month = "6",
day = "15",
doi = "10.1038/nature04724",
language = "English",
volume = "441",
pages = "885--889",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "7095",

}

TY - JOUR

T1 - Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice

AU - Hara, Taichi

AU - Nakamura, Kenji

AU - Matsui, Makoto

AU - Yamamoto, Akitsugu

AU - Nakahara, Yohko

AU - Suzuki-Migishima, Rika

AU - Yokoyama, Minesuke

AU - Mishima, Kenji

AU - Saito, Ichiro

AU - Okano, Hideyuki

AU - Mizushima, Noboru

PY - 2006/6/15

Y1 - 2006/6/15

N2 - Autophagy is an intracellular bulk degradation process through which a portion of the cytoplasm is delivered to lysosomes to be degraded. Although the primary role of autophagy in many organisms is in adaptation to starvation, autophagy is also thought to be important for normal turnover of cytoplasmic contents, particularly in quiescent cells such as neurons. Autophagy may have a protective role against the development of a number of neurodegenerative diseases. Here we report that loss of autophagy causes neurodegeneration even in the absence of any disease-associated mutant proteins. Mice deficient for Atg5 (autophagy-related 5) specifically in neural cells develop progressive deficits in motor function that are accompanied by the accumulation of cytoplasmic inclusion bodies in neurons. In Atg5-/- cells, diffuse, abnormal intracellular proteins accumulate, and then form aggregates and inclusions. These results suggest that the continuous clearance of diffuse cytosolic proteins through basal autophagy is important for preventing the accumulation of abnormal proteins, which can disrupt neural function and ultimately lead to neurodegeneration.

AB - Autophagy is an intracellular bulk degradation process through which a portion of the cytoplasm is delivered to lysosomes to be degraded. Although the primary role of autophagy in many organisms is in adaptation to starvation, autophagy is also thought to be important for normal turnover of cytoplasmic contents, particularly in quiescent cells such as neurons. Autophagy may have a protective role against the development of a number of neurodegenerative diseases. Here we report that loss of autophagy causes neurodegeneration even in the absence of any disease-associated mutant proteins. Mice deficient for Atg5 (autophagy-related 5) specifically in neural cells develop progressive deficits in motor function that are accompanied by the accumulation of cytoplasmic inclusion bodies in neurons. In Atg5-/- cells, diffuse, abnormal intracellular proteins accumulate, and then form aggregates and inclusions. These results suggest that the continuous clearance of diffuse cytosolic proteins through basal autophagy is important for preventing the accumulation of abnormal proteins, which can disrupt neural function and ultimately lead to neurodegeneration.

UR - http://www.scopus.com/inward/record.url?scp=33745192802&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33745192802&partnerID=8YFLogxK

U2 - 10.1038/nature04724

DO - 10.1038/nature04724

M3 - Article

VL - 441

SP - 885

EP - 889

JO - Nature

JF - Nature

SN - 0028-0836

IS - 7095

ER -