ABSTRACT Apoptosis, or cellular suicide, is important for normal development and tissue homeostasis, but too much or too little apoptosis can also cause disease1,2. The family of cysteine

proteases, the so-called caspases, are critical mediators of programmed cell death3, and thus far 14 family members have been identified. Some of these, such as caspase-8 (refs 4, 5),

mediate signal transduction downstream of death receptors located on the plasma membrane. Others, such as caspase-9 (ref. 6), mediate apoptotic signals after mitochondrial damage. Stress in

the endoplasmic reticulum (ER) can also result in apoptosis7. Here we show that caspase-12 is localized to the ER and activated by ER stress, including disruption of ER calcium homeostasis

amyloid-β protein but not by staurosporine or trophic factor deprivation. Thus, caspase-12 mediates an ER-specific apoptosis pathway and may contribute to amyloid-β neurotoxicity. Access

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SIMILAR CONTENT BEING VIEWED BY OTHERS AΒ42 OLIGOMERS TRIGGER SYNAPTIC LOSS THROUGH CAMKK2-AMPK-DEPENDENT EFFECTORS COORDINATING MITOCHONDRIAL FISSION AND MITOPHAGY Article Open access 01

August 2022 MOLECULAR MECHANISMS OF CELL DEATH IN NEUROLOGICAL DISEASES Article Open access 07 June 2021 SORCIN IS AN EARLY MARKER OF NEURODEGENERATION, CA2+ DYSREGULATION AND ENDOPLASMIC

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A. Yagi for pMCIDT-A; T. Noda for PGK-neo plasmids; J. L. Goldstein for anti-caspase-3; T. Rapoport for anti-TRAPα; S. Nagata for W4 cells; M. Yuan for technical help in the preparation of

Aβ, and S.-J. Kang for providing caspase-11 mutant mice. This work was supported in part by grants from Hoechst-Marion-Roussel and Harvard Medical School project (to J.Y.) and from Human

Frontier Science Program Organization and TOYOBO Biotechnology Foundation (to T.N.). AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Department of Cell Biology, Harvard Medical School, 240

Longwood Avenue, Boston, 02115, Massachusetts, USA Toshiyuki Nakagawa, Hong Zhu & Junying Yuan * Biodesign Research Group, RIKEN (the Institute of Physical and Chemical Research), 2-1

Hirosawa, Wako, 351-0198, Saitama, Japan Nobuhiro Morishima * Cardiovascular Research Center, Massachusetts General Hospital, 129 13th Street, Charlestown, 02119, Massachussetts, USA En Li *

Department of Neurology, Harvard Medical School and Children's Hospital, Enders 260, 300 Longwood Avenue, Boston, 02115, Massachussetts, USA Jin Xu & Bruce A. Yankner Authors *

Toshiyuki Nakagawa View author publications You can also search for this author inPubMed Google Scholar * Hong Zhu View author publications You can also search for this author inPubMed 

Google Scholar * Nobuhiro Morishima View author publications You can also search for this author inPubMed Google Scholar * En Li View author publications You can also search for this author

inPubMed Google Scholar * Jin Xu View author publications You can also search for this author inPubMed Google Scholar * Bruce A. Yankner View author publications You can also search for this

author inPubMed Google Scholar * Junying Yuan View author publications You can also search for this author inPubMed Google Scholar CORRESPONDING AUTHOR Correspondence to Junying Yuan.

RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Nakagawa, T., Zhu, H., Morishima, N. _et al._ Caspase-12 mediates endoplasmic-reticulum-specific

apoptosis and cytotoxicity by amyloid-β. _Nature_ 403, 98–103 (2000). https://doi.org/10.1038/47513 Download citation * Received: 19 October 1999 * Accepted: 19 November 1999 * Issue Date:

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