Target intelligence / Profile preview

Kidney and brain protein (KIBRA) (KIBRA)

Target
KIBRA
Molecular classification
Scaffold protein, WWC domain-containing protein, Postsynaptic density protein
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Overview

Kidney and brain protein (KIBRA), encoded by the WWC1 gene, is a postsynaptic scaffolding protein primarily expressed in the brain and kidneys. In the central nervous system, KIBRA plays a critical role in regulating synaptic plasticity and memory by stabilizing protein kinase Mzeta (PKMζ) and facilitating the trafficking of AMPA receptors to the postsynaptic membrane. Recent research has identified KIBRA as a novel target for synapse repair in Alzheimer's disease and other tauopathies, where its levels are significantly depleted in the brain but elevated in the cerebrospinal fluid. Therapeutic strategies focusing on restoring KIBRA signaling, such as the use of truncated CT-KIBRA peptides, have shown promise in reversing cognitive deficits and restoring synaptic function in animal models of neurodegeneration. Unlike many current Alzheimer's therapies that target amyloid or tau accumulation, KIBRA-based approaches aim to directly repair the synaptic damage that underlies memory loss.

Other names
WWC1Kidney and brain proteinKIBRAHBeAg-binding protein 3WWC domain-containing protein 1
02

Mechanism of action

Stabilization of PKMζ to promote postsynaptic AMPAR trafficking and restore synaptic plasticity

03

Biological functions

Synaptic plasticityLong-term potentiation (LTP)Memory formationPostsynaptic scaffoldingAMPAR traffickingHippo signaling pathway
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Disease associations

Alzheimer's diseaseTauopathyCognitive impairmentDementiaSchizophrenia
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Safety considerations

Potential off-target effects in the kidneyBlood-brain barrier penetration for peptide-based therapiesModulation of the Hippo signaling pathway (oncogenic potential)
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Interacting drugs

CT-KIBRA (experimental peptide)

1 more in the full profile.

07

Biomarkers

Cerebrospinal fluid (CSF) KIBRA levelsBrain tissue KIBRA expression

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