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Article
Probing backbone hydrogen bonding in PDZ/ligand interactions by protein amide-to-ester mutations
PDZ domains are scaffolding modules in protein–protein interactions that mediate numerous physiological functions by interacting canonically with the C-terminus or non-canonically with an internal motif of pro...
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Article
Open AccessEvolution of the p53-MDM2 pathway
The p53 signalling pathway, which controls cell fate, has been extensively studied due to its prominent role in tumor development. The pathway includes the tumor supressor protein p53, its vertebrate paralogs ...
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Article
Open AccessEfficient and inexpensive transient expression of multispecific multivalent antibodies in Expi293 cells
Immunotherapy is a very fast expanding field within drug discovery and, hence, rapid and inexpensive expression of antibodies would be extremely valuable. Antibodies are, however, difficult to express. Multifu...
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Article
Open AccessEfficient clearance of Aβ protofibrils in AβPP-transgenic mice treated with a brain-penetrating bifunctional antibody
Amyloid-β (Aβ) immunotherapy is one of the most promising disease-modifying strategies for Alzheimer’s disease (AD). Despite recent progress targeting aggregated forms of Aβ, low antibody brain penetrance rema...
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Article
Open AccessNovel multivalent design of a monoclonal antibody improves binding strength to soluble aggregates of amyloid beta
Amyloid-β (Aβ) immunotherapy is a promising therapeutic strategy in the fight against Alzheimer’s disease (AD). A number of monoclonal antibodies have entered clinical trials for AD. Some of them have failed d...
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Article
Open AccessPinpointing Brain TREM2 Levels in Two Mouse Models of Alzheimer’s Disease
The triggering receptor expressed on myeloid cells 2 (TREM2) is expressed by brain microglia. Microglial activation, as observed in Alzheimer’s disease (AD) as well as in transgenic mice expressing human amylo...
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Article
Open AccessA Brain-Targeting Bispecific-Multivalent Antibody Clears Soluble Amyloid-Beta Aggregates in Alzheimer’s Disease Mice
Amyloid-β (Aβ) oligomers and protofibrils are suggested to be the most neurotoxic Aβ species in Alzheimer’s disease (AD). Hence, antibodies with strong and selective binding to these soluble Aβ aggregates are ...
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Article
Open AccessBlood–brain barrier penetrating neprilysin degrades monomeric amyloid-beta in a mouse model of Alzheimer’s disease
Aggregation of the amyloid-β (Aβ) peptide in the brain is one of the key pathological events in Alzheimer’s disease (AD). Reducing Aβ levels in the brain by enhancing its degradation is one possible strategy t...
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Article
Open AccessIntroducing or removing heparan sulfate binding sites does not alter brain uptake of the blood–brain barrier shuttle scFv8D3
The blood–brain barrier (BBB) greatly limits the delivery of protein-based drugs into the brain and is a major obstacle for the treatment of brain disorders. Targeting the transferrin receptor (TfR) is a strat...
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Article
Open AccessLong-term effects of immunotherapy with a brain penetrating Aβ antibody in a mouse model of Alzheimer’s disease
Brain-directed immunotherapy is a promising strategy to target amyloid-β (Aβ) deposits in Alzheimer’s disease (AD). In the present study, we compared the therapeutic efficacy of the Aβ protofibril targeting an...
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Article
Open AccessAltered amyloid-β structure markedly reduces gliosis in the brain of mice harboring the Uppsala APP deletion
Deposition of amyloid beta (Aβ) into plaques is a major hallmark of Alzheimer’s disease (AD). Different amyloid precursor protein (APP) mutations cause early-onset AD by altering the production or aggregation pro...
