LMNA Protein

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LMNA Protein

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LMNA Protein

Overview

<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">LMNA Protein</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td><strong>LMNA</strong></td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>LMNA</td>
</tr>
<tr>
<td class="label">Type</td>
<td>Protein</td>
</tr>
<tr>
<td class="label">UniProt</td>
<td><a href="https://www.uniprot.org/uniprot/?query=LMNA" target="_blank">Search UniProt</a></td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/ad" style="color:#ef9a9a">AD</a>, <a href="/wiki/ali" style="color:#ef9a9a">ALI</a>, <a href="/wiki/als" style="color:#ef9a9a">ALS</a>, <a href="/wiki/alzheimer's-disease" style="color:#ef9a9a">ALZHEIMER'S DISEASE</a>, <a href="/wiki/ami" style="color:#ef9a9a">AMI</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">510 edges</a></td>
</tr>
</table>

Lmna Protein plays an important role in the study of neurodegenerative diseases. This page provides comprehensive information about this topic, including its mechanisms, significance in disease processes, and therapeutic implications.

Pathway Diagram

...

LMNA Protein

Overview

<table class="infobox infobox-protein">
<tr>
<th class="infobox-header" colspan="2">LMNA Protein</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td><strong>LMNA</strong></td>
</tr>
<tr>
<td class="label">Full Name</td>
<td>LMNA</td>
</tr>
<tr>
<td class="label">Type</td>
<td>Protein</td>
</tr>
<tr>
<td class="label">UniProt</td>
<td><a href="https://www.uniprot.org/uniprot/?query=LMNA" target="_blank">Search UniProt</a></td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/ad" style="color:#ef9a9a">AD</a>, <a href="/wiki/ali" style="color:#ef9a9a">ALI</a>, <a href="/wiki/als" style="color:#ef9a9a">ALS</a>, <a href="/wiki/alzheimer's-disease" style="color:#ef9a9a">ALZHEIMER'S DISEASE</a>, <a href="/wiki/ami" style="color:#ef9a9a">AMI</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">510 edges</a></td>
</tr>
</table>

Lmna Protein plays an important role in the study of neurodegenerative diseases. This page provides comprehensive information about this topic, including its mechanisms, significance in disease processes, and therapeutic implications.

Pathway Diagram

Mermaid diagram (expand to render)

Introduction

LMNA encodes lamin A and lamin C, two key nuclear intermediate filament proteins that form the nuclear lamina beneath the inner nuclear membrane[@gruenbaum2015]. The nuclear lamina provides structural support to the nucleus, organizes chromatin domains, and regulates essential cellular processes including DNA replication, transcription, and nuclear envelope integrity. LMNA mutations are associated with a spectrum of human diseases collectively called laminopathies, which include Hutchinson-Gilford progeria syndrome (HGPS), Emery-Dreifuss muscular dystrophy (EDMD), dilated cardiomyopathy (DCM), and mandibuloacral dysplasia (MAD)[@bonne1999]. Importantly, lamin dysfunction has been increasingly recognized as a contributing factor in neurodegenerative diseases including amyotrophic lateral sclerosis (ALS), Parkinson's disease (PD), and Alzheimer's disease (AD)[@kim2023].

Gene and Protein Structure

Gene Organization

The LMNA gene is located on chromosome 1q22 and spans approximately 9 kb of genomic DNA. It consists of 12 exons and produces multiple splice variants through alternative splicing:

Exon 1: Encodes the head domain
Exons 2-7: Encode the central rod domain (α-helical coiled-coil)
Exons 8-12: Encode the tail domain including the nuclear localization signal (NLS)

Protein Architecture

Lamin A/C proteins share common structural features:

N-terminal Head Domain (1-33 aa)

Highly basic, unstructured
Contains phosphorylation sites (Ser22, Ser392)
Involved in chromatin binding

Central Rod Domain (34-386 aa)

Seven α-helical segments (1A, 1B, 2A, 2B, 2C, 2D, 2E)
Coiled-coil structure
Mediates dimerization via parallel registration

C-terminal Tail Domain (387-664 aa)

Contains nuclear localization signal (NLS)
Ig-fold domain for protein interactions
CAAX motif for farnesylation (lamin A only)
Proteolytic cleavage site (lamin A maturation)

Isoforms

Lamin A: 664 aa, 72 kDa - undergoes farnesylation and proteolytic processing
Lamin C: 572 aa, 65 kDa - alternative splicing, no CAAX motif
Lamin AΔ50: Common HGPS mutation, missing 50 amino acids

Normal Cellular Functions

Nuclear Structure and Integrity

Lamin A/C provides mechanical stability to the nucleus through:

Nuclear lamina meshwork: Intermediate filament network at the nuclear periphery

Chromatin organization: Interactions with heterochromatin and lamina-associated domains (LADs)

Nuclear pore complex anchoring: Supports nuclear envelope infrastructure

Linker of nucleoskeleton and cytoskeleton (LINC) complex: Connects to cytoplasmic cytoskeleton

Gene Regulation

Lamin A/C modulates gene expression through:

Epigenetic regulation: Controls heterochromatin distribution
Transcriptional regulation: Interacts with transcription factors (SRF, MOK2)
DNA damage response: Facilitates repair machinery recruitment
Replication timing: Influences replication origin selection

Nuclear Envelope Functions

Nuclear import/export: Anchors nuclear pore complexes
Centrosome positioning: Important for cell division
Mechanical signaling: Transduces mechanical forces via LINC complex
[Autophagy](/entities/autophagy) regulation: Nuclear envelope turnover

Role in Neurodegenerative Diseases

Amyotrophic Lateral Sclerosis (ALS)

Evidence for LMNA involvement:

LMNA mutations cause EDMD with ALS-like features
Nuclear envelope abnormalities observed in ALS patient cells
Impaired nucleocytoplasmic transport in LMNA-deficient motor [neurons](/entities/neurons)
[TDP-43](/proteins/tdp-43) pathology associated with lamin dysfunction

Mechanisms:

Nuclear import disruption: ALS-causing mutations impair nuclear pore function

DNA damage accumulation: Defective DNA repair in motor neurons

Mechanical stress: Motor neurons experience high mechanical stress

Proteostasis failure: Impaired protein quality control systems

Mitochondrial dysfunction: Altered nuclear-mitochondrial communication

Parkinson's Disease

Evidence:

LMNA expression altered in PD brains
Nuclear envelope defects in PD patient-derived neurons
Interaction with Parkin (PRKN) signaling pathway

Mechanisms:

PINK1/Parkin pathway: LMNA degradation in mitophagy

[α-Synuclein](/proteins/alpha-synuclein) interaction: Nuclear envelope permeability

Oxidative stress: LMNA vulnerable to oxidative damage

Alzheimer's Disease

Evidence:

Altered lamin A/C expression in AD brains
Nuclear envelope irregularities in AD neurons
Lamin pathology in AD post-mortem tissue

Mechanisms:

[Aβ](/proteins/amyloid-beta) toxicity: Amyloid-beta damages nuclear envelope

[Tau](/proteins/tau) pathology: Hyperphosphorylated [tau](/proteins/tau) affects nuclear lamina

Genomic instability: DNA damage accumulation

Huntington's Disease

LMNA mislocalization in HD models
Nuclear envelope permeability
Transcriptional dysregulation

Molecular Interactions

Nuclear Envelope Proteins

EMD (Emerin): Inner nuclear membrane protein, EDMD causative
MAN1 (LEM domain containing 2): Antagonizes TGF-β signaling
LBR (Lamin B Receptor): Cholesterol biosynthesis
SUN1/2: LINC complex components
NESPRIN-1/2: Outer nuclear membrane partners

Chromatin Proteins

Lamin B Receptor (LBR): Heterochromatin anchoring
HDAC3: Transcriptional repression
RBBP4/7: Histone deacetylase complexes
BAF (Barrier-to-autointegration factor): DNA binding

Signaling Pathways

TGF-β signaling: SMAD pathway regulation
Wnt/β-catenin: Transcriptional co-activation
MAPK/ERK: Stress-responsive signaling
p53 pathway: DNA damage response

Therapeutic Approaches

Pharmacological Strategies

Farnesyltransferase Inhibitors

Lonafarnib: FDA-approved for HGPS
Tipifarnib: Being investigated for laminopathies
Mechanism: Prevents abnormal lamin A farnesylation

[mTOR](/entities/mtor) Inhibitors

Rapamycin: Enhances autophagy of mutant lamin
Everolimus: Being studied in clinical trials

[HDAC](/entities/hdac-enzymes) Inhibitors

Sodium butyrate: Improves lamin A/C expression
Vorinostat: Modifies chromatin accessibility

Gene Therapy

AAV vectors: Deliver wild-type LMNA
CRISPR-Cas9: Correct LMNA mutations
Antisense oligonucleotides: Modulate LMNA splicing

Small Molecule Modulators

Retinoic acid: Regulates LMNA expression
Selisistat: SIRT1 activator, affects lamin function
Natural compounds: Curcumin, resveratrol effects

Diagnostic and Prognostic Significance

Biomarkers

Serum lamin A/C fragments: Disease progression markers
Nuclear morphology: Biomarker in patient fibroblasts
Gene expression profiles: LMNA dysregulation signatures

Clinical Implications

LMNA mutation carriers: Monitor for neurodegeneration
Nuclear envelope defects: Early diagnostic indicators
Therapeutic targets for neuroprotection

Research Methods

Experimental Models

Patient-derived fibroblasts: iPSC motor neurons
Mouse models: Lmna knockout and mutant strains
C. elegans: Homologous gene (lmn-1)
Drosophila: Lamin Dm0

Detection Techniques

Western blot: Protein expression analysis
Immunofluorescence: Nuclear envelope localization
Electron microscopy: Nuclear morphology
ChIP-seq: Chromatin interactions
Hi-C: 3D genome organization

Overview

Lmna Protein plays an important role in the study of neurodegenerative diseases. This page provides comprehensive information about this topic, including its mechanisms, significance in disease processes, and therapeutic implications.

Background

The study of Lmna 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.

External Links

[PubMed](https://pubmed.ncbi.nlm.nih.gov/) - Biomedical literature
[Alzheimer's Disease Neuroimaging Initiative](https://adni.loni.usc.edu/) - Research data
[Allen Brain Atlas](https://brain-map.org/) - Brain gene expression data

Cross-References

[LMNA Gene](/proteins/lmna-protein)
[ALS Disease](/diseases/amyotrophic-lateral-sclerosis)
[Parkinson's Disease](/diseases/parkinsons-disease)
[Nuclear Envelope](/entities/nuclear-envelope)
[Cell Types Index](/cell-types)
[Proteins Index](/proteins)

References

[Gruenbaum Y, Foisner R, "Lamins: nuclear intermediate filament proteins with fundamental functions in nuclear mechanics and genome regulation." Annu Rev Biochem (2015)](https://pubmed.ncbi.nlm.nih.gov/25747401/)

[Bonne G, Di Barletta MR, Varnous S, et al, "Mutations in the gene encoding lamin A/C cause autosomal dominant Emery-Dreifuss muscular dystrophy." Nat Genet (1999)](https://pubmed.ncbi.nlm.nih.gov/10080184/)

[Kim Y, Zheng Y, "Nuclear lamina dysfunction and its implication in neurodegeneration." Cell Mol Neurobiol (2023)](https://pubmed.ncbi.nlm.nih.gov/37266894/)

[Dobson NR, Cleveland TE, "Lamin A/C and the immune system." J Cell Sci (2020)](https://pubmed.ncbi.nlm.nih.gov/32350067/)

[Liu GH, Suzuki K, Qu J, et al, "Selected approaches to modeling Hutchinson-Gilford progeria syndrome with iPSCs." Stem Cell Res (2014)](https://pubmed.ncbi.nlm.nih.gov/24268182/)

[Zhang J, Lian Q, Zhu G, et al, "A human iSC model of Hutchinson-Gilford progeria reveals vascular smooth muscle and mesenchymal stem cell defects." Cell Stem Cell (2011)](https://pubmed.ncbi.nlm.nih.gov/21185248/)

[Goldman RD, Shumaker DK, Erdos MR, et al, "Accumulation of mutant lamin A causes progressive changes in nuclear architecture in Hutchinson-Gilford progeria syndrome." Proc Natl Acad Sci U S A (2004)](https://pubmed.ncbi.nlm.nih.gov/15184648/)

[Scaffidi P, Misteli T, "Lamin A-dependent misregulation of adult stem cells associated with accelerated ageing." Nat Cell Biol (2008)](https://pubmed.ncbi.nlm.nih.gov/18311132/)

[De Sandre-Giovannoli A, Bernard R, Cau P, et al, "Lamin a truncation in Hutchinson-Gilford progeria." Science (2003)](https://pubmed.ncbi.nlm.nih.gov/12702811/)

[Eriksson M, Brown WT, Gordon LB, et al, "Recurrent de novo point mutations in lamin A cause Hutchinson-Gilford progeria syndrome." Nature (2003)](https://pubmed.ncbi.nlm.nih.gov/12714972/)

Pathway Diagram

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

Mermaid diagram (expand to render)

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Related Entities

LMNA

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kg_node_id	LMNA
entity_type	protein
origin_type	v1_polymorphic_backfill
source_table	wiki_pages
wiki_page_id	wp-bbcf4ebc5e7a
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📊 Evidence Profile Foundational

Evidence Balance

+0%

Certainty

65%

Debates

0

Incoming

13

Outgoing

51

0 supporting 0 contradicting 0 neutral

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📗 Cite This Artifact

LMNA Protein

LMNA Protein

Overview

Pathway Diagram

LMNA Protein

Overview

Pathway Diagram

Introduction

Gene and Protein Structure

Gene Organization

Protein Architecture

Isoforms

Normal Cellular Functions

Nuclear Structure and Integrity

Gene Regulation

Nuclear Envelope Functions

Role in Neurodegenerative Diseases

Amyotrophic Lateral Sclerosis (ALS)

Parkinson's Disease

Alzheimer's Disease

Huntington's Disease

Molecular Interactions

Nuclear Envelope Proteins

Chromatin Proteins

Signaling Pathways

Therapeutic Approaches

Pharmacological Strategies

Gene Therapy

Small Molecule Modulators

Diagnostic and Prognostic Significance

Biomarkers

Clinical Implications

Research Methods

Experimental Models

Detection Techniques

Overview

Background

See Also

External Links

Cross-References

References

Pathway Diagram

💬 Discussion