TGFB1 — Transforming Growth Factor Beta 1

TGFB1 (Transforming Growth Factor Beta 1)

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">TGFB1 — Transforming Growth Factor Beta 1</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>TGFB1</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>19q13.2</td>
</tr>
<tr>
<td class="label">Official Full Name</td>
<td>Transforming Growth Factor Beta 1</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>P01137</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000127616</td>
</tr>
<tr>
<td class="label">Gene Type</td>
<td>Protein coding</td>
</tr>
<tr>
<td class="label">Length</td>
<td>23,431 bp (genomic)</td>
</tr>
<tr>
<td class="label">Protein Length</td>
<td>390 amino acids (latent propeptide + 112 aa mature)</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">ALS</a>, <a href="/wiki/aging" style="color:#ef9a9a">Aging</a>, <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></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">371 edges</a></td>
</tr>
</table>

Overview

TGFB1 (Transforming Growth Factor Beta 1)

<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">TGFB1 — Transforming Growth Factor Beta 1</th>
</tr>
<tr>
<td class="label">Gene Symbol</td>
<td>TGFB1</td>
</tr>
<tr>
<td class="label">Chromosomal Location</td>
<td>19q13.2</td>
</tr>
<tr>
<td class="label">Official Full Name</td>
<td>Transforming Growth Factor Beta 1</td>
</tr>
<tr>
<td class="label">UniProt ID</td>
<td>P01137</td>
</tr>
<tr>
<td class="label">Ensembl ID</td>
<td>ENSG00000127616</td>
</tr>
<tr>
<td class="label">Gene Type</td>
<td>Protein coding</td>
</tr>
<tr>
<td class="label">Length</td>
<td>23,431 bp (genomic)</td>
</tr>
<tr>
<td class="label">Protein Length</td>
<td>390 amino acids (latent propeptide + 112 aa mature)</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">ALS</a>, <a href="/wiki/aging" style="color:#ef9a9a">Aging</a>, <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></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">371 edges</a></td>
</tr>
</table>

Overview

TGFB1 encodes Transforming Growth Factor Beta 1, a key cytokine with complex roles in neuroinflammation, neuroprotection, and synaptic plasticity. Dysregulation of TGFB1 signaling is implicated in multiple neurodegenerative diseases including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS)[@tesseur2006].

Gene Information

Protein Structure and Function

TGF-beta1 is synthesized as a preproprotein consisting of:

• Signal peptide: 1-29 aa
• Latency-associated peptide (LAP): 30-249 aa
• Mature TGF-beta1: 250-390 aa (112 aa active cytokine)

Activation Mechanism

TGF-beta1 requires activation from its latent form:

• Proteases (MMP-2, MMP-9, plasmin)
• Integrins (alpha-v-beta-6, alpha-v-beta-8)
• [Reactive oxygen species](/entities/reactive-oxygen-species)
• Acidic microenvironment

Signaling Pathway

Active TGF-beta1 binds to:

Role in Neurodegeneration

Alzheimer's Disease

TGF-beta1 has complex, stage-dependent roles in AD[@caraci2012]:

• Neuroprotective Effects: Promotes neuronal survival, modulates amyloid metabolism
• Microglial Modulation: Can shift [microglia](/cell-types/microglia-neuroinflammation) toward a protective phenotype
• [Blood-Brain Barrier](/entities/blood-brain-barrier): Regulates BBB integrity and function
• Synaptic Plasticity: Influences hippocampal synaptic function

Parkinson's Disease

In PD, TGF-beta1 signaling is implicated in[@sanches2021]:

• Dopaminergic Neuroprotection: TGF-beta1 can protect dopaminergic [neurons](/entities/neurons)
• Neuroinflammation: Modulates microglial activation states
• [Alpha-Synuclein](/proteins/alpha-synuclein): May influence aggregation and clearance

Amyotrophic Lateral sclerosis

TGF-beta1 dysregulation is observed in ALS[@phatnani2013]:

• Increased TGF-beta1 in serum and CSF of ALS patients
• Motor neuron vulnerability
• Glial cell involvement

Genetic Associations

Single Nucleotide Polymorphisms (SNPs)

• rs1800469 (-509C>T): Associated with TGF-beta1 expression levels
• rs1982073 (T29C): Affects protein secretion
• rs1800470 (L10P): Alters bioactivity

Expression Changes in Disease

• Elevated TGFB1 in AD [hippocampus](/brain-regions/hippocampus) and [cortex](/brain-regions/cortex)
• Increased in PD substantia nigra
• Upregulated in ALS motor cortex and spinal cord

Therapeutic Implications

TGF-beta-Based Therapies

• Recombinant TGF-beta1: Being explored for neuroprotection
• Small Molecule Agonists: Targeting TGF-beta receptors
• Gene Therapy: AAV-mediated delivery in preclinical models

Challenges

• Complex dose-dependent effects
• Peripheral vs. central nervous system delivery
• Need for targeted approaches

Related Proteins and Pathways

Receptors

• [TGFBR1](/proteins/tgfbr1-protein) - Type I receptor
• [TGFBR2](/proteins/tgfbr2-protein) - Type II receptor

Signaling Molecules

• SMAD2 - R-SMAD
• SMAD3 - R-SMAD
• SMAD4 - Co-SMAD

Related Mechanisms

• [Neuroinflammation](/mechanisms/neuroinflammation-microglia)
• [Blood-Brain Barrier](/mechanisms/blood-brain-barrier)
• [TGF-beta Signaling](/mechanisms/tgf-beta-signaling)

See Also

• [TGFB1 Protein](/proteins/tgfbr1-protein)
• [Neuroinflammation](/mechanisms/neuroinflammation-microglia)
• [Blood-Brain Barrier](/mechanisms/blood-brain-barrier)
• [TGF-beta Signaling](/mechanisms/tgf-beta-signaling)

External Links

• [Ensembl: ENSG00000127616](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000127616)
• [NCBI Gene: TGFB1](https://www.ncbi.nlm.nih.gov/gene/?term=TGFB1)
• [GeneCards: TGFB1](https://www.genecards.org/cgi-bin/carddisp.pl?gene=TGFB1)
• [OMIM: TGFB1](https://omim.org/search?search=TGFB1)
• [Allen Brain Atlas: TGFB1](https://human.brain-map.org/microarray/search/show?search_term=TGFB1)

TGFβ in Immune Modulation

Neuroinflammation

TGFβ effects on immune cells[@tesseur2006] Microglial modulation:

• [Anti-inflammatory](/clinical-trials/ntrx-07-neurotherapia-nct07058688)
• [Phagocytosis](/therapeutics/phagocytosis-modulation-therapy)
• Surveillance

References

TGFβ1: Comprehensive Analysis

Signal Transduction

Intracellular pathways[@tesseur2006] SMAD-dependent:

• Receptor activation
• SMAD complex formation
• Nuclear translocation

• - PI3K/AKT
• Rho GTPases

Receptor Biology

Type I, II, and III receptors[@sanches2021] Ligand binding:

• TGFβ1, β2, β3
• Latent TGFβ binding
• Activation mechanisms

• Receptor traffi- Endocytosis
• D

TGFβ in the Nervous System

Neurodevelopment

Developmental functions[^5][^6]:

Neurulation:

• Neural tube formation
• Dorsal-ventral patterning
• Cell fate decisions

• Proliferation
• Migration
• Differentiation

Synaptic Function

Activity modulation[^7][^8]:

Synaptic plasticity:

• LTP/LTD effects
• Homeostatic plasticity
• Behavior

• GABAergic signaling
• Glutamate receptors
• Excitability

Neuroinflammation

Microglial Modulation

TGFβ effects on glia[^9][^10]:

Anti-inflammatory:

• M2 polarization
• Cytokine production
• Phagocytosis

• Trophic support
• Tissue repair
• Aβ clearance

Autoimmune Diseases

MS and EAE[^11][^12]:

Pro-inflammatory effects:

• Th17 differentiation
• Demyelination
• Pathology

• Neutralizing antibodies
• Receptor kinase inhibitors
• Cell therapy

Tissue Repair

Wound Healing

Regeneration mechanisms[^13][^14]:

Inflammation phase:

• Immune cell recruitment
• Cytokine release
• Debridement

• Fibroblast proliferation
• Extracellular matrix
• Angiogenesis

• Collagen deposition
• Scar formation
• Maturation

Fibrosis

Pathological scarring[^15][^16]:

Mechanisms:

• Myofibroblast differentiation
• ECM accumulation
• Contraction

• TGFβ neutralization
• Kinase inhibitors
• Gene therapy

References

[^5[^7

Related Hypotheses

From the [SciDEX Exchange](/exchange) — scored by multi-agent debate

• [Ocular Immune Privilege Extension](/hypothesis/h-6a065252) — <span style="color:#ffd54f;font-weight:600">0.47</span> · Target: FOXP3/TGFB1
• [Microbiome-Derived Tryptophan Metabolite Neuroprotection](/hypothesis/h-f9c6fa3f) — <span style="color:#ff8a65;font-weight:600">0.39</span> · Target: AHR, IL10, TGFB1

Pathway Diagram

Pathway Diagram

The following diagram shows the key molecular relationships involving TGFB1 — Transforming Growth Factor Beta 1 discovered through SciDEX knowledge graph analysis: