 |
 Previous Article | Next Article 
The Journal of Neuroscience, September 15, 2000, 20(18):6898-6906
Cathepsin D Deficiency Induces Lysosomal Storage with Ceroid
Lipofuscin in Mouse CNS Neurons
Masato
Koike1,
Hiroshi
Nakanishi2,
Paul
Saftig3,
Junji
Ezaki5,
Kyoko
Isahara1,
Yoshiyuki
Ohsawa1,
Walter
Schulz-Schaeffer4,
Tsuyoshi
Watanabe1,
Satoshi
Waguri1,
Satoshi
Kametaka1,
Masahiro
Shibata1,
Kenji
Yamamoto2,
Eiki
Kominami5,
Christoph
Peters6,
Kurt
von Figura3, and
Yasuo
Uchiyama1
1 Department of Cell Biology and Neurosciences,
Osaka University Graduate School of Medicine, Suita, Osaka 565-0871, Japan, 2 Department of Pharmacology, Faculty of Dentistry,
Kyushu University, Fukuoka 812-8582, Japan, 3 Center for
Biochemistry and Molecular Cell Biology and 4 Department of
Neuropathology, Göttingen University, 37073 Göttingen,
Germany, 5 Department of Biochemistry, Juntendo University
School of Medicine, 2-1-1 Hongo, Tokyo, Japan, and
6 Medizin, Universitätsklinik, Abteilung I, Freiburg
University, 79106 Freiburg, Germany
Cathepsin D-deficient (CD /) mice have been shown to manifest
seizures and become blind near the terminal stage [approximately postnatal day (P) 26]. We therefore examined the morphological, immunocytochemical, and biochemical features of CNS
tissues of these mice. By electron microscopy,
autophagosome/autolysosome-like bodies containing part of the
cytoplasm, granular osmiophilic deposits, and fingerprint profiles were
demonstrated in the neuronal perikarya of CD/ mouse brains after
P20. Autophagosomes and granular osmiophilic deposits were detected in
neurons at P0 but were few in number, whereas they increased in the
neuronal perikarya within days after birth. Some large-sized neurons
having autophagosome/autolysosome-like bodies in the perikarya appeared
in the CNS tissues, especially in the thalamic region and the cerebral
cortex, at P17. These lysosomal bodies occupied the perikarya of almost
all neurons in CD/ mouse brains obtained from P23 until the
terminal stage. Because these neurons exhibited autofluorescence, it
was considered that ceroid lipofuscin may accumulate in lysosomal
structures of CD/ neurons. Subunit c of mitochondrial ATP synthase
was found to accumulate in the lysosomes of neurons, although the activity of tripeptidyl peptidase-I significantly increased in the
brain. Moreover, neurons near the terminal stage were often shrunken
and possessed irregular nuclei through which small dense chromatin
masses were scattered. These results suggest that the CNS neurons in
CD/ mice show a new form of lysosomal accumulation disease with a
phenotype resembling neuronal ceroid lipofuscinosis.
Key words:
cathepsin D; knockout mouse; CNS neurons; ceroid
lipofuscin; subunit c of mitochondrial F1F0ATPase; lysosomal storage; neuronal ceroid lipofuscinosis
Copyright © 2000 Society for Neuroscience 0270-6474/00/20186898-09$05.00/0
This article has been cited by other articles:
|
|
|
|
 
V. Sagulenko, D. Muth, E. Sagulenko, T. Paffhausen, M. Schwab, and F. Westermann
Cathepsin D protects human neuroblastoma cells from doxorubicin-induced cell death
Carcinogenesis,
October 1, 2008;
29(10):
1869 - 1877.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Wei, S.-J. Kim, Z. Zhang, P.-C. Tsai, K. E. Wisniewski, and A. B. Mukherjee
ER and oxidative stresses are common mediators of apoptosis in both neurodegenerative and non-neurodegenerative lysosomal storage disorders and are alleviated by chemical chaperones
Hum. Mol. Genet.,
February 14, 2008;
17(4):
469 - 477.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Koike, M. Shibata, M. Tadakoshi, K. Gotoh, M. Komatsu, S. Waguri, N. Kawahara, K. Kuida, S. Nagata, E. Kominami, et al.
Inhibition of Autophagy Prevents Hippocampal Pyramidal Neuron Death after Hypoxic-Ischemic Injury
Am. J. Pathol.,
February 1, 2008;
172(2):
454 - 469.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. A. Nixon
Autophagy, amyloidogenesis and Alzheimer disease
J. Cell Sci.,
December 1, 2007;
120(23):
4081 - 4091.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. J. Shacka, B. J. Klocke, C. Young, M. Shibata, J. W. Olney, Y. Uchiyama, P. Saftig, and K. A. Roth
Cathepsin D Deficiency Induces Persistent Neurodegeneration in the Absence of Bax-Dependent Apoptosis
J. Neurosci.,
February 21, 2007;
27(8):
2081 - 2090.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Yanagawa, T. Tsukuba, T. Nishioku, Y. Okamoto, K. Okamoto, R. Takii, Y. Terada, K. I. Nakayama, T. Kadowaki, and K. Yamamoto
Cathepsin E Deficiency Induces a Novel Form of Lysosomal Storage Disorder Showing the Accumulation of Lysosomal Membrane Sialoglycoproteins and the Elevation of Lysosomal pH in Macrophages
J. Biol. Chem.,
January 19, 2007;
282(3):
1851 - 1862.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C.-H. Tang, J.-W. Lee, M. G. Galvez, L. Robillard, S. E. Mole, and H. A. Chapman
Murine cathepsin f deficiency causes neuronal lipofuscinosis and late-onset neurological disease.
Mol. Cell. Biol.,
March 1, 2006;
26(6):
2309 - 2316.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. J. Shacka and K. A. Roth
Cathepsin Deficiency as a Model for Neuronal Ceroid Lipofuscinoses
Am. J. Pathol.,
December 1, 2005;
167(6):
1473 - 1476.
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Koike, M. Shibata, S. Waguri, K. Yoshimura, I. Tanida, E. Kominami, T. Gotow, C. Peters, K. von Figura, N. Mizushima, et al.
Participation of Autophagy in Storage of Lysosomes in Neurons from Mouse Models of Neuronal Ceroid-Lipofuscinoses (Batten Disease)
Am. J. Pathol.,
December 1, 2005;
167(6):
1713 - 1728.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
Y. Yasuda, T. Tsukuba, K. Okamoto, T. Kadowaki, and K. Yamamoto
The Role of the Cathepsin E Propeptide in Correct Folding, Maturation and Sorting to the Endosome
J. Biochem.,
November 1, 2005;
138(5):
621 - 630.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Esselens, V. Oorschot, V. Baert, T. Raemaekers, K. Spittaels, L. Serneels, H. Zheng, P. Saftig, B. De Strooper, J. Klumperman, et al.
Presenilin 1 mediates the turnover of telencephalin in hippocampal neurons via an autophagic degradative pathway
J. Cell Biol.,
September 27, 2004;
166(7):
1041 - 1054.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. A. Nixon
Niemann-Pick Type C Disease and Alzheimer's Disease: The APP-Endosome Connection Fattens Up
Am. J. Pathol.,
March 1, 2004;
164(3):
757 - 761.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Kametaka, M. Shibata, K. Moroe, S. Kanamori, Y. Ohsawa, S. Waguri, P. J. Sims, K. Emoto, M. Umeda, and Y. Uchiyama
Identification of Phospholipid Scramblase 1 as a Novel Interacting Molecule with beta -Secretase (beta -Site Amyloid Precursor Protein (APP) Cleaving Enzyme (BACE))
J. Biol. Chem.,
April 18, 2003;
278(17):
15239 - 15245.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
U. Felbor, B. Kessler, W. Mothes, H. H. Goebel, H. L. Ploegh, R. T. Bronson, and B. R. Olsen
Neuronal loss and brain atrophy in mice lacking cathepsins B and L
PNAS,
June 11, 2002;
99(12):
7883 - 7888.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Nishioku, K. Hashimoto, K. Yamashita, S.-Y. Liou, Y. Kagamiishi, H. Maegawa, N. Katsube, C. Peters, K. von Figura, P. Saftig, et al.
Involvement of Cathepsin E in Exogenous Antigen Processing in Primary Cultured Murine Microglia
J. Biol. Chem.,
February 8, 2002;
277(7):
4816 - 4822.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Nakanishi, J. Zhang, M. Koike, T. Nishioku, Y. Okamoto, E. Kominami, K. von Figura, C. Peters, K. Yamamoto, P. Saftig, et al.
Involvement of Nitric Oxide Released from Microglia-Macrophages in Pathological Changes of Cathepsin D-Deficient Mice
J. Neurosci.,
October 1, 2001;
21(19):
7526 - 7533.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
