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In cathepsin D-deficient (CD-/-) and cathepsins B and L double-deficient (CB-/-CL-/-) mice, abnormal vacuolar structures accumulate in neurons of the brains. Many of these structures resemble autophagosomes in which part of the cytoplasm is retained but their precise nature and biogenesis remain unknown. We show here how autophagy contributes to the(More)
Although of clinical importance, little is known about the mechanism of seizure in neuronal ceroid lipofuscinosis (NCL). In the present study, we have attempted to elucidate the mechanism underlying the seizure of cathepsin D-deficient (CD-/-) mice that show a novel type of lysosomal storage disease with a phenotype resembling late infantile NCL. In(More)
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(More)
To understand the mechanisms of retinal atrophy in cathepsin D-deficient mice, the postnatal development of their retinae was analyzed. TUNEL-positive cells appeared abundantly in the outer nuclear layer (ONL) and slightly in the inner nuclear layer (INL). Nitric oxide synthase (NOS) was induced in microglial cells which invaded retinal layers and(More)
Metachromatic leukodystrophy is a lysosomal sphingolipid storage disorder caused by the deficiency of arylsulfatase A. The disease is characterized by progressive demyelination, causing various neurologic symptoms. Since no naturally occurring animal model of the disease is available, we have generated arylsulfatase A-deficient mice. Deficient animals store(More)
TOPCONS (http://topcons.net/) is a widely used web server for consensus prediction of membrane protein topology. We hereby present a major update to the server, with some substantial improvements, including the following: (i) TOPCONS can now efficiently separate signal peptides from transmembrane regions. (ii) The server can now differentiate more(More)
Transient images help to analyze light transport in scenes. Besides two spatial dimensions, they are resolved in time of flight. Cost-efficient approaches for their capture use amplitude modulated continuous wave lidar systems but typically take more than a minute of capture time. We propose new techniques for measurement and reconstruction of transient(More)
Nitric oxide (NO) and peroxynitrite, which are produced by activated microglia, are responsible for accelerated neurodegeneration in cathepsin D-deficient (CD-/-) mice. To elucidate the mechanisms by which microglia are initially activated in CD-/- mice, we analyzed the possible relationship between lysosomal storage and microglial activation. In CD-/-(More)
The inherited epilepsy Unverricht-Lundborg disease (EPM1) is caused by loss-of-function mutations in the cysteine protease inhibitor, cystatin B. Because cystatin B inhibits a class of lysosomal cysteine proteases called cathepsins, we hypothesized that increased proteolysis by one or more of these cathepsins is likely to be responsible for the seizure,(More)
Neuropeptide Y (NPY) functions as a peptide neurotransmitter and as a neuroendocrine hormone. The active NPY peptide is generated in secretory vesicles by proteolytic processing of proNPY. Novel findings from this study show that cathepsin L participates as a key proteolytic enzyme for NPY production in secretory vesicles. Notably, NPY levels in cathepsin L(More)