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Target intelligence / Profile preview
Pyroglutamate-modified Amyloid Beta (N3pG-Aβ)
- Target
- N3pG-Aβ
- Molecular classification
- Peptide, Modified Peptide, Amyloid beta peptide
01
Overview
Pyroglutamate-modified amyloid beta (N3pG-Aβ) is a form of amyloid beta peptide that has undergone N-terminal truncation and subsequent modification, resulting in the formation of a pyroglutamate residue at position 3. This modification increases aggregation propensity, neurotoxicity, and resistance to degradation compared to full-length Aβ peptides. It is highly prevalent in Alzheimer’s disease brains and correlates with disease severity. Donanemab is a therapeutic antibody that specifically targets this modified form of amyloid beta.
- Other names
- Aβ(pE3-x)pE-Aβ(3–42)AbetaN3(pE)-x
02
Mechanism of action
Monoclonal antibody targeting pyroglutamate-modified amyloid beta, promoting plaque clearance.
03
Biological functions
AggregationNeurotoxicityAmyloid plaque formationSynaptic dysfunctionTau pathology inductionNeurodegeneration
04
Disease associations
Alzheimer's DiseaseDown's Syndrome
05
Safety considerations
Microhemorrhages (observed with some anti-Aβ antibodies, but less so with Donanemab in preclinical studies)Amyloid-related imaging abnormalities (ARIA)
06
Interacting drugs
Donanemab
07
Biomarkers
N3pG-Aβ levels in brain tissueN3pG-Aβ levels in cerebrospinal fluid
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