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Your search keyword '"Stefan Knackmuss"' showing total 2 results
Start Over Author "Stefan Knackmuss" Journal scientific reports
2 results on '"Stefan Knackmuss"'

1. The 37kDa/67kDa Laminin Receptor acts as a receptor for Aβ42 internalization

Author

Stefan Knackmuss, Katarina Jovanovic, Stefan Weiss, Danielle Gonsalves, Bianca Da Costa Dias, Kiashanee Moodley, Marc S. Weinberg, Melvyn Little, and Uwe Reusch

Subjects
Ribosomal Proteins, media_common.quotation_subject, Apoptosis, Biology, Endocytosis, Article, Small hairpin RNA, Pathogenesis, Receptors, Laminin, Downregulation and upregulation, medicine, Humans, Internalization, Receptor, media_common, Multidisciplinary, Amyloid beta-Peptides, Protein Stability, HEK 293 cells, Neurotoxicity, medicine.disease, Molecular biology, Peptide Fragments, Cell biology, Protein Transport, HEK293 Cells, lipids (amino acids, peptides, and proteins), Protein Binding
Abstract

Neuronal loss is a major neuropathological hallmark of Alzheimer's disease (AD). The associations between soluble Aβ oligomers and cellular components cause this neurotoxicity. The 37 kDa/67 kDa laminin receptor (LRP/LR) has recently been implicated in Aβ pathogenesis. In this study the mechanism underlying the pathological role of LRP/LR was elucidated. Forsters Resonance Energy Transfer (FRET) revealed that LRP/LR and Aβ form a biologically relevant interaction. The ability of LRP/LR to form stable associations with endogenously shed Aβ was confirmed by pull down assays and Aβ-ELISAs. Antibody blockade of this association significantly lowered Aβ42 induced apoptosis. Furthermore, antibody blockade and shRNA mediated downregulation of LRP/LR significantly hampered Aβ42 internalization. These results suggest that LRP/LR is a receptor for Aβ42 internalization, mediating its endocytosis and contributing to the cytotoxicity of the neuropeptide by facilitating intra-cellular Aβ42 accumulation. These findings recommend anti-LRP/LR specific antibodies and shRNAs as potential therapeutic tools for AD treatment.

Published
2014

2. Anti-LRP/LR specific antibodies and shRNAs impede amyloid beta shedding in Alzheimer's disease

Author

Uwe Reusch, Stefan Weiss, Kiashanee Moodley, Stefan Knackmuss, Clement Penny, Bianca Da Costa Dias, Danielle Gonsalves, Melvyn Little, Katarina Jovanovic, and Marc S. Weinberg

Subjects
Amyloid beta, Intracellular Space, Article, Cell Line, Receptors, Laminin, Amyloid beta-Protein Precursor, Alzheimer Disease, mental disorders, medicine, Amyloid precursor protein, Humans, RNA, Small Interfering, Multidisciplinary, Amyloid beta-Peptides, biology, Cell Membrane, P3 peptide, Antibodies, Monoclonal, medicine.disease, Molecular biology, Transport protein, Biochemistry of Alzheimer's disease, Protein Transport, Alpha secretase, biology.protein, Cancer research, lipids (amino acids, peptides, and proteins), RNA Interference, Alzheimer's disease, Amyloid Precursor Protein Secretases, Amyloid precursor protein secretase, Protein Binding
Abstract

Alzheimer's disease (AD) is the most prevalent form of dementia. The amyloid beta (Aβ) peptide is the predominant candidate aetiological agent and is generated through the sequential proteolytic cleavage of the Amyloid Precursor Protein (APP) by beta (β) and gamma (γ) secretases. Since the cellular prion protein (PrP(c)) has been shown to regulate Aβ shedding, we investigated whether the cellular receptor for PrP(c), namely the 37 kDa/67 kDa Laminin Receptor (LRP/LR) played a role in Aβ shedding. Here we show that LRP/LR co-localises with the AD relevant proteins APP, β- and γ-secretase, respectively. Antibody blockage and shRNA knock-down of LRP/LR reduces Aβ shedding, due to impediment of β-secretase activity, rather than alteration of APP, β- and γ-secretase levels. These findings indicate that LRP/LR contributes to Aβ shedding and recommend anti-LRP/LR specific antibodies and shRNAs as novel therapeutic tools for AD treatment.

Published
2013

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