Journal ArticleDOI
Protein processing in lysosomes: the new therapeutic target in neurodegenerative disease
TLDR
It is now appropriate to consider therapeutic manipulation of the lysosomal system as an approach to treatment for the treatment of neurodegeneration.About:
This article is published in The Lancet.The article was published on 1992-07-18. It has received 55 citations till now. The article focuses on the topics: ATG16L1 & Neurodegeneration.read more
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Prion Diseases of Humans and Animals: Their Causes and Molecular Basis
TL;DR: The appearance of a novel human prion disease, variant CJD, and the clear experimental evidence that it is caused by exposure to BSE has highlighted the need to understand the molecular basis of prion propagation, pathogenesis, andThe barriers limiting intermammalian transmission.
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Reversible Conversion of Monomeric Human Prion Protein Between Native and Fibrilogenic Conformations
Graham S. Jackson,Laszlo L. P. Hosszu,Laszlo L. P. Hosszu,Aisling Power,Andrew F. Hill,John M. Kenney,Helen R. Saibil,C. J. Craven,Jonathan P. Waltho,Anthony R. Clarke,Anthony R. Clarke,John Collinge +11 more
TL;DR: Conditions were established in which recombinant human PrP could switch between the native alpha conformation, characteristic of PrPC, and a compact, highly soluble, monomeric form rich in beta structure, providing a molecular mechanism for prion propagation.
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Surfactant properties of Alzheimer's A beta peptides and the mechanism of amyloid aggregation.
TL;DR: Results suggest that the structure of A beta has the same type of axial amphipathic organization as detergent molecules and that the same principles that govern micelle formation may also apply to A beta aggregation and amyloid fibril self-assembly.
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Molecular neurology of prion disease
TL;DR: There is increasing recognition that fundamental processes involved in prion propagation – seeded aggregation of misfolded host proteins – are of far wider significance, not least in understanding the commoner neurodegenerative diseases that pose such a major and increasing challenge for healthcare in an ageing population.
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The abnormal isoform of the prion protein accumulates in late-endosome-like organelles in scrapie-infected mouse brain.
TL;DR: ME7 scrapie‐infected mouse brain was used to show that proteinase K‐resistant PrPsc is enriched in subcellular structures which contain the cation‐independent mannose 6‐phosphate receptor, ubiquitin‐protein conjugates, β‐glucuronidase, and cathepsin B, termed late endosome‐like organelles.
References
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Molecular biology of prion diseases
TL;DR: Understanding prion diseases may advance investigations of other neurodegenerative disorders and of the processes by which neurons differentiate, function for decades, and then grow senescent.
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Scrapie prion protein contains a phosphatidylinositol glycolipid
TL;DR: Observations indicate that PrPC is anchored to the cell surface by the glycolipid, which is derived from PrPSc by limited proteolysis at the amino terminus.
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Targeting of cell-surface β-amyloid precursor protein to lysosomes: alternative processing into amyloid-bearing fragments
TL;DR: A second processing pathway for βAPP is defined and it is suggested that it may be responsible for generating amyloid-bearing fragments in Alzheimer's disease.
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A role for a 70-kilodalton heat shock protein in lysosomal degradation of intracellular proteins
TL;DR: A 73-kilodalton protein was found to bind to peptide regions that target intracellular proteins for lysosomal degradation in response to serum withdrawal, and sequences of two internal peptides of the 73-kD protein confirm that it is a member of this family.
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Ubiquitin is a component of paired helical filaments in Alzheimer's disease
TL;DR: To obtain direct evidence that ubiquitin is a component of PHF, PHF were treated with concentrated formic acid and digested with lysylendopeptidase; ubiquitIn-derived peptides were then identified by reversed-phase high-performance liquid chromatography.