Journal ArticleDOI
Murine model of Niemann-Pick C disease: mutation in a cholesterol homeostasis gene.
Stacie K. Loftus,Jill A. Morris,Eugene D. Carstea,Jessie Z. Gu,Christiano Cummings,Anthony Brown,Jane S. Ellison,Kousaku Ohno,Melissa A. Rosenfeld,Danilo A. Tagle,Peter G. Pentchev,William J. Pavan +11 more
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TLDR
The mouse model may provide an important resource for studying the role of NPC1 in cholesterol homeostasis and neurodegeneration and for assessing the efficacy of new drugs for NP-C disease.Abstract:
An integrated human-mouse positional candidate approach was used to identify the gene responsible for the phenotypes observed in a mouse model of Niemann-Pick type C (NP-C) disease. The predicted murine NPC1 protein has sequence homology to the putative transmembrane domains of the Hedgehog signaling molecule Patched, to the cholesterol-sensing regions of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and SREBP cleavage-activating protein (SCAP), and to the NPC1 orthologs identified in human, the nematode Caenorhabditis elegans, and the yeast Saccharomyces cerevisiae. The mouse model may provide an important resource for studying the role of NPC1 in cholesterol homeostasis and neurodegeneration and for assessing the efficacy of new drugs for NP-C disease.read more
Citations
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Hedgehog signaling in animal development: paradigms and principles.
TL;DR: In their screen for mutations that disrupt the Drosophila larval body plan, these authors identified several that cause the duplication of denticles and an accompanying loss of naked cuticle, characteristic of the posterior half of each segment.
Journal ArticleDOI
Tau protein isoforms, phosphorylation and role in neurodegenerative disorders
TL;DR: Tau proteins are the major constituents of intraneuronal and glial fibrillar lesions described in Alzheimer's disease and numerous neurodegenerative disorders referred as 'tauopathies' as discussed by the authors.
Journal ArticleDOI
Niemann-Pick C1 Like 1 protein is critical for intestinal cholesterol absorption.
Scott W. Altmann,Harry R. Davis,Li-ji Zhu,Xiaorui Yao,Lizbeth M. Hoos,Glen Tetzloff,Sai Prasad N. Iyer,Maureen Maguire,Andrei Golovko,Ming Zeng,Luquan Wang,Nicholas J. Murgolo,Michael P. Graziano +12 more
TL;DR: It is shown that Niemann-Pick C1Like 1(NPC1L1) protein plays a critical role in the absorption of intestinal cholesterol, and resides in an ezetimibe-sensitive pathway responsible for intestinal cholesterol absorption.
Journal ArticleDOI
Niemann-Pick C1 disease gene: homology to mediators of cholesterol homeostasis.
Eugene D. Carstea,Jill A. Morris,Katherine G. Coleman,Stacie K. Loftus,Dana Zhang,Christiano Cummings,Jessie Z. Gu,Melissa A. Rosenfeld,William J. Pavan,David B. Krizman,James W. Nagle,M H Polymeropoulos,Stephen L. Sturley,Yiannis A. Ioannou,Maureen E. Higgins,Marcella E. Comly,Adele Cooney,Anthony Brown,Christine R. Kaneski,E. Joan Blanchette-Mackie,Nancy K. Dwyer,Edward B. Neufeld,Ta-Yuan Chang,Laura Liscum,Jerome F. Strauss,Kousaku Ohno,Marsha Zeigler,Rivka Carmi,J Sokol,David Markie,Raymond R. O'Neill,O. P. van Diggelen,Milan Elleder,Marc C. Patterson,Roscoe O. Brady,Marie T. Vanier,Peter G. Pentchev,Danilo A. Tagle +37 more
TL;DR: Transfection of NP-C fibroblasts with wild-type NPC1 cDNA resulted in correction of their excessive lysosomal storage of LDL cholesterol, thereby defining the critical role of NPC1 in regulation of intracellular cholesterol trafficking.
Journal ArticleDOI
A proteolytic pathway that controls the cholesterol content of membranes, cells, and blood
TL;DR: These regulated proteolytic cleavage reactions are ultimately responsible for controlling the level of cholesterol in membranes, cells, and blood.
References
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Basic Local Alignment Search Tool
TL;DR: A new approach to rapid sequence comparison, basic local alignment search tool (BLAST), directly approximates alignments that optimize a measure of local similarity, the maximal segment pair (MSP) score.
Journal ArticleDOI
Human Homolog of patched, a Candidate Gene for the Basal Cell Nevus Syndrome
Ronald L. Johnson,Alana L. Rothman,Jingwu Xie,Lisa V. Goodrich,John W. Bare,Jeannette M. Bonifas,Anthony G. Quinn,Richard M. Myers,David R. Cox,Ervin H. Epstein,Matthew P. Scott +10 more
TL;DR: Heritable mutations in BCNS patients and a somatic mutation in a sporadic BCC were identified in a human homolog of the Drosophila patched (ptc) gene, which appears to be crucial for proper embryonic development and for tumor suppression.
Journal ArticleDOI
Niemann-Pick C1 disease gene: homology to mediators of cholesterol homeostasis.
Eugene D. Carstea,Jill A. Morris,Katherine G. Coleman,Stacie K. Loftus,Dana Zhang,Christiano Cummings,Jessie Z. Gu,Melissa A. Rosenfeld,William J. Pavan,David B. Krizman,James W. Nagle,M H Polymeropoulos,Stephen L. Sturley,Yiannis A. Ioannou,Maureen E. Higgins,Marcella E. Comly,Adele Cooney,Anthony Brown,Christine R. Kaneski,E. Joan Blanchette-Mackie,Nancy K. Dwyer,Edward B. Neufeld,Ta-Yuan Chang,Laura Liscum,Jerome F. Strauss,Kousaku Ohno,Marsha Zeigler,Rivka Carmi,J Sokol,David Markie,Raymond R. O'Neill,O. P. van Diggelen,Milan Elleder,Marc C. Patterson,Roscoe O. Brady,Marie T. Vanier,Peter G. Pentchev,Danilo A. Tagle +37 more
TL;DR: Transfection of NP-C fibroblasts with wild-type NPC1 cDNA resulted in correction of their excessive lysosomal storage of LDL cholesterol, thereby defining the critical role of NPC1 in regulation of intracellular cholesterol trafficking.
Journal ArticleDOI
Cholesterol Modification of Hedgehog Signaling Proteins in Animal Development
TL;DR: It is reported that cholesterol is the lipophilic moiety covalently attached to the amino- terminal signaling domain during autoprocessing and that the carboxyl-terminal domain acts as an intramolecular cholesterol transferase.
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Niemann-Pick C1 disease gene: homology to mediators of cholesterol homeostasis.
Eugene D. Carstea,Jill A. Morris,Katherine G. Coleman,Stacie K. Loftus,Dana Zhang,Christiano Cummings,Jessie Z. Gu,Melissa A. Rosenfeld,William J. Pavan,David B. Krizman,James W. Nagle,M H Polymeropoulos,Stephen L. Sturley,Yiannis A. Ioannou,Maureen E. Higgins,Marcella E. Comly,Adele Cooney,Anthony Brown,Christine R. Kaneski,E. Joan Blanchette-Mackie,Nancy K. Dwyer,Edward B. Neufeld,Ta-Yuan Chang,Laura Liscum,Jerome F. Strauss,Kousaku Ohno,Marsha Zeigler,Rivka Carmi,J Sokol,David Markie,Raymond R. O'Neill,O. P. van Diggelen,Milan Elleder,Marc C. Patterson,Roscoe O. Brady,Marie T. Vanier,Peter G. Pentchev,Danilo A. Tagle +37 more