Summary: A new study reveals the crucial role of the protein Contactin-4 (CNTN4) in neuron development, impacting both neurodevelopmental disorders and Alzheimer’s disease. Researchers found that CNTN4, linked to autism, interacts with the Alzheimer’s disease-linked protein APP, affecting the growth of neurons in the cerebral cortex.
This discovery highlights a co-dependent relationship essential for healthy brain development. The findings offer new insights into the overlap between developmental and neurodegenerative diseases.
Highlights:
- Key protein:CNTN4 is crucial for neuron development and linked to autism and Alzheimer’s disease.
- Protein interaction: CNTN4 and APP interaction is vital for healthy brain function.
- Impact on neurons: Elimination of CNTN4 alters the growth of neurons in the cerebral cortex.
Source: University of Exeter
New research has shed light on the complex interplay between cellular proteins and their impact on neurons in neurodevelopmental disorders and Alzheimer’s disease.
A new study led by the University of Exeter and published in Royal Society Open Biology discovered the key role played by the Contactin-4 protein (encoded by the CNTN4 gene) in the formation of neurons.
Researchers began studying CNTN4 because it was known for its role in autism, but its functional roles were not well understood. The team explored how CNTN4 functions in the brain, particularly its interactions with proteins involved in neurodegenerative diseases such as Alzheimer’s disease.
For the first time, researchers studied mice whose CNTN4 gene had been inactivated in the cortex, the region of the brain responsible for key functions such as memory, thinking and reasoning. They found that neurons developed differently in the cortex region.
Researchers have demonstrated for the first time in human cells the interaction between the CNTN4 and APP genes, a gene strongly linked to Alzheimer’s disease, revealing a codependent relationship essential for brain development, and in particular for healthy growth of neurons.
They found that CNTN4 not only contributes to neural elongation in the frontal cortex region of the brain, but that CNTN4 expression is also regulated via a relationship with APP.
Using studies on genetically modified human cells, the team also discovered that there is a complex interaction between CNTN4 and APP. If CNTN4 is eliminated, APP levels decrease, but not to zero. Scientists believe that APP could compensate for the loss of CNTN4, and vice versa.
Lead author of the study, Dr Rosemary Bamford, from the University of Exeter Medical School, said: “It was quite remarkable to discover that CNTN4, a gene linked to developmental processes, also plays a role in the modulation of factors involved in Alzheimer’s disease.
“This intersection of developmental and neurodegenerative pathways offers exciting new insights into the broader implications of these proteins.”
Lead author Dr Asami Oguro-Ando, from the University of Exeter School of Medicine, said: “Looking forward, my group is keen to further dissect the molecular mechanisms underlying the interaction between CNTN4 and APP and explore their broader implications for disorders like Alzheimer’s disease and autism. Spectrum disorder.
“Our next steps are to clarify the impact of CNTN4-APP interaction on neuronal activity. Understanding this interaction is crucial because it represents a fundamental step toward a comprehensive understanding of neurodevelopmental and neurodegenerative disorders.
About this research news on autism and Alzheimer’s disease
Author: Louise Vennells
Source: University of Exeter
Contact: Louise Vennells – University of Exeter
Picture: Image is credited to Neuroscience News
Original research: Free access.
“CNTN4 modulates neuronal elongation through interaction with APP” by Rosemary Bamford et al. Royal Society Open Biology
Abstract
CNTN4 modulates neuronal elongation through interaction with APP
The neuronal cell adhesion molecule contactin-4 (CNTN4) is genetically associated with autism spectrum disorder (ASD) and other psychiatric disorders.
Cntn4-deficient mouse models have already shown that CNTN4 plays an important role in axon guidance and synaptic plasticity in the hippocampus.
However, the pathogenesis and functional role of CNTN4 in the cortex have not yet been investigated.
Our study revealed a reduction in cortical thickness of the motor cortex of Cntn4 −/− mice, but migration and differentiation of cortical cells were not affected. Significant morphological changes were observed in neurons in the M1 region of the motor cortex, indicating that CNTN4 is also involved in the morphology and spine density of motor cortex neurons.
Additionally, mass spectrometry analysis identified an interaction partner for CNTN4, confirming an interaction between CNTN4 and amyloid precursor protein (APP). Human CNTN4 and/or APP knockout cells revealed a relationship between CNTN4 and APP.
This study demonstrates that CNTN4 contributes to cortical development and that binding and interaction with APP controls neuronal elongation. This is an important discovery for understanding the physiological function of APP, a key protein in Alzheimer’s disease.
The link between CNTN4 and APP, involved in neurodevelopment, is essential for healthy nerve growth.
News Source : neurosciencenews.com
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