Reelin Protein

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protein876 wordssynced 2026-04-02

Reelin Protein

<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">Reelin Protein</th>
</tr>
<tr>
<td class="label">Approach</td>
<td>Status</td>
</tr>
<tr>
<td class="label">Recombinant Reelin protein</td>
<td>Research</td>
</tr>
<tr>
<td class="label">Reelin-enhancing compounds</td>
<td>Preclinical</td>
</tr>
<tr>
<td class="label">Gene therapy</td>
<td>Preclinical</td>
</tr>
<tr>
<td class="label">Peptide analogs</td>
<td>Research</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">ALS</a>, <a href="/wiki/alzheimer" style="color:#ef9a9a">ALZHEIMER</a>, <a href="/wiki/alzheimer's-disease" style="color:#ef9a9a">ALZHEIMER'S DISEASE</a>, <a href="/wiki/aging" style="color:#ef9a9a">Aging</a>, <a href="/wiki/als" style="color:#ef9a9a">Als</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">153 edges</a></td>
</tr>
</table>

Pathway Diagram

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Reelin Protein

Pathway Diagram

Mermaid diagram (expand to render)

Knowledge graph relationships for REELIN (316 total edges in KG)

Introduction

Reelin Protein is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.

Overview

Reelin is a large extracellular matrix protein that plays critical roles in neuronal migration, cortical layer formation, and synaptic plasticity during brain development and in the adult brain. Reelin signaling through [ApoE](/genes/apoe) receptors modulates dendritic spine morphology and synaptic function. Reelin dysfunction is implicated in Alzheimer's disease and neuropsychiatric disorders. [@weeber2002]

This protein is involved in: [@botellalpez2006]

Neuronal migration: Essential for cortical layer formation
Synaptic plasticity: Regulates spine density and function
Dendritic development: Controls dendritic arborization
Disease associations: Alzheimer's disease, autism, schizophrenia, lissencephaly

Reelin is a large extracellular glycoprotein that plays essential roles in neuronal migration, synaptic plasticity, and cognitive function. It is a key regulator of brain development and is critically involved in the pathogenesis of Alzheimer's Disease and neuropsychiatric disorders. [@grayson2005]

Structure

Gene and Protein Overview

Gene Symbol: RELN
Gene ID: 5649
Chromosome: 7q22.1
Protein Length: 3,460 amino acids
Molecular Weight: ~388 kDa (one of the largest secreted proteins)
UniProt ID: P78536
PDB Structures: 7JX6, 7JX7 (reelin domains)

Reelin is a member of the reelin family of extracellular matrix proteins. It contains an N-terminal signal peptide, followed by a Reelin domain, 8 EGF-like repeats, and 3 Reelin repeat domains (R1-R3), each containing 300 amino acids.

Domain Organization

Signal peptide (aa 1-27): Secretory pathway targeting
Reelin N-terminal domain (aa 28-189): Receptor binding
EGF-like domains (aa 190-327): Protein-protein interactions
Reelin repeat domains R1-R3 (aa 328-3460): Core functional domains
R1: aa 328-711
R2: aa 712-1095
R3: aa 1096-1480
C-terminal region (aa 1481-3460): Full-length reelin contains 8 repeats

Normal Function

Neuronal Migration

Reelin is best known for its role in cortical lamination:[@darcangelo1995]

Secreted by Cajal-Retzius cells in the marginal zone
Guides radial migration of [neurons](/entities/neurons) during development
Controls proper positioning of pyramidal neurons in [cortex](/brain-regions/cortex)
Essential for layer formation in [hippocampus](/brain-regions/hippocampus) and cerebellum

Synaptic Plasticity

In the adult brain, Reelin modulates:[@weeber2002]

[Long-term potentiation](/mechanisms/long-term-potentiation) (LTP) and depression (LTD)
Dendritic spine morphology and density
Synaptic vesicle release probability
[NMDA](/entities/nmda-receptor) receptor trafficking and function

Cognitive Function

Reelin is essential for:

Spatial learning and memory
Contextual fear conditioning
Social behavior
Mood regulation

Role in Disease

Alzheimer's Disease

Reelin is significantly implicated in AD pathogenesis:[@botellalpez2006]

Reelin expression is reduced in AD brains, particularly in the [entorhinal cortex](/brain-regions/entorhinal-cortex) and hippocampus
Amyloid-beta (Aβ) oligomers suppress Reelin expression
Reduced Reelin contributes to synaptic dysfunction and memory impairment
Reelin interacts with APP and affects [amyloid precursor protein](/entities/app-protein) processing
Reelin-containing neurons are vulnerable in AD

Reelin-[Aβ](/proteins/amyloid-beta) Interaction:

Aβ oligomers bind to Reelin receptors, disrupting downstream signaling
This leads to impaired synaptic plasticity
Contributes to early memory deficits before significant amyloid deposition

Schizophrenia and Bipolar Disorder

Reelin is a major susceptibility factor:[@grayson2005]

RELN promoter hypermethylation reduces expression
Reduced Reelin protein in prefrontal cortex
Genetic variants associated with disease risk
Developmental disruption of cortical layering

Autism Spectrum Disorder

Reduced Reelin levels in some ASD patients
Mouse models show Reelin haploinsufficiency leads to ASD-like behaviors
Interaction with autism-linked genes (CNTNAP2, FLNB)

Epilepsy

Reelin mutations cause lissencephaly in humans
Altered Reelin signaling contributes to epileptogenesis
Reelin supplementation reduces seizure frequency in models

Therapeutic Targeting

Reelin-Based Therapies

Clinical Trials

No active clinical trials for Reelin-targeted therapy as of 2026
Biomarker development ongoing (Reelin in CSF)

Mechanism-Based Strategies

Aβ-Reelin interaction blockers: Prevent Aβ-mediated Reelin dysfunction
Dab1 activators: Downstream signaling molecule enhancement
LRP8/ApoER2 agonists: Reelin receptor stimulation

Background

The study of Reelin Protein has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.

Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.

Brain Atlas Resources

The following resources from the Allen Brain Atlas provide expression and connectivity data for this protein/gene:

[Allen Human Brain Atlas - Gene Expression](https://human.brain-map.org/microarray/search/show?search_term=RELN): Searchable gene expression database from adult human brain
[Allen Brain Atlas - RNA Sequencing](https://human.brain-map.org/rnasearch): RNA sequencing data across brain regions
[Allen Cell Type Atlas](https://celltypes.brain-map.org/): Single-cell transcriptomic data for cell type classification
[Allen Mouse Brain Atlas](https://mouse.brain-map.org/): Comprehensive mouse brain gene expression database
[BrainSpan Atlas of the Developing Human Brain](https://www.brainspan.org/): Developmental expression data across brain regions and ages

External Links

[UniProt P78536](https://www.uniprot.org/uniprot/P78536)
[GeneCards RELN](https://www.genecards.org/cgi-bin/carddisp.pl?gene=RELN)
[PubMed Reelin](https://pubmed.ncbi.nlm.nih.gov/?term=Reelin+Alzheimer+neurodegeneration)

References

[D'Arcangelo G, et al, (1995) (1995)](https://pubmed.ncbi.nlm.nih.gov/7643043/)

[Weeber EJ, et al, (2002) (2002)](https://pubmed.ncbi.nlm.nih.gov/11741897/)

[Botella-López A, et al, (2006) (2006)](https://pubmed.ncbi.nlm.nih.gov/16478526/)

[Grayson DR, et al, (2005) (2005)](https://pubmed.ncbi.nlm.nih.gov/15677321/)

Pathway Diagram

The following diagram shows the key molecular relationships involving Reelin Protein discovered through SciDEX knowledge graph analysis:

Mermaid diagram (expand to render)

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Reelin Protein

Reelin Protein

Pathway Diagram

Reelin Protein

Pathway Diagram

Introduction

Overview

Structure

Gene and Protein Overview

Domain Organization

Normal Function

Neuronal Migration

Synaptic Plasticity

Cognitive Function

Role in Disease

Alzheimer's Disease

Schizophrenia and Bipolar Disorder

Autism Spectrum Disorder

Epilepsy

Therapeutic Targeting

Reelin-Based Therapies

Clinical Trials

Mechanism-Based Strategies

Background

See Also

Brain Atlas Resources

External Links

References

Pathway Diagram