SYNGR3 Gene
Introduction
<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">SYNGR3 Gene</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td>SYNGR3</td>
</tr>
<tr>
<td class="label">Full name</td>
<td>Synaptophysin-3 / Synaptogyrin-3</td>
</tr>
<tr>
<td class="label">Chromosome</td>
<td>16p13.2</td>
</tr>
<tr>
<td class="label">NCBI Gene</td>
<td>[SYNGR3 Gene](https://www.ncbi.nlm.nih.gov/gene/102724)</td>
</tr>
<tr>
<td class="label">Ensembl</td>
<td>[ENSG00000134152](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000134152)</td>
</tr>
<tr>
<td class="label">Encoded protein</td>
<td>SYNGR3 Protein (synaptophysin-3)</td>
</tr>
<tr>
<td class="label">Related pathways</td>
<td>[Synaptic Vesicle Trafficking](/mechanisms/synaptic-vesicle-trafficking), [Protein Aggregation](/mechanisms/protein-aggregation), [Alpha-Synucleinopathy](/mechanisms/alpha-synuclein-pathology)</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/dementia" style="color:#ef9a9a">Dementia</a>, <a href="/wiki/ms" style="color:#ef9a9a">Ms</a>, <a href="/wiki/parkinson" style="color:#ef9a9a">Parkinson</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">11 edges</a></td>
</tr>
</table>
...SYNGR3 Gene
Introduction
<table class="infobox infobox-gene">
<tr>
<th class="infobox-header" colspan="2">SYNGR3 Gene</th>
</tr>
<tr>
<td class="label">Symbol</td>
<td>SYNGR3</td>
</tr>
<tr>
<td class="label">Full name</td>
<td>Synaptophysin-3 / Synaptogyrin-3</td>
</tr>
<tr>
<td class="label">Chromosome</td>
<td>16p13.2</td>
</tr>
<tr>
<td class="label">NCBI Gene</td>
<td>[SYNGR3 Gene](https://www.ncbi.nlm.nih.gov/gene/102724)</td>
</tr>
<tr>
<td class="label">Ensembl</td>
<td>[ENSG00000134152](https://www.ensembl.org/Homo_sapiens/Gene/Summary?g=ENSG00000134152)</td>
</tr>
<tr>
<td class="label">Encoded protein</td>
<td>SYNGR3 Protein (synaptophysin-3)</td>
</tr>
<tr>
<td class="label">Related pathways</td>
<td>[Synaptic Vesicle Trafficking](/mechanisms/synaptic-vesicle-trafficking), [Protein Aggregation](/mechanisms/protein-aggregation), [Alpha-Synucleinopathy](/mechanisms/alpha-synuclein-pathology)</td>
</tr>
<tr>
<td class="label">Associated Diseases</td>
<td><a href="/wiki/als" style="color:#ef9a9a">Als</a>, <a href="/wiki/dementia" style="color:#ef9a9a">Dementia</a>, <a href="/wiki/ms" style="color:#ef9a9a">Ms</a>, <a href="/wiki/parkinson" style="color:#ef9a9a">Parkinson</a></td>
</tr>
<tr>
<td class="label">KG Connections</td>
<td><a href="/atlas" style="color:#4fc3f7">11 edges</a></td>
</tr>
</table>
SYNGR3 encodes synaptophysin-3 (also known as synaptogyrin-3), a synaptic vesicle protein that plays a critical role in Parkinson's disease pathogenesis. Recent research has identified SYNGR3 as a key promoter of [alpha-synuclein](/proteins/alpha-synuclein) aggregation and neurotoxicity, positioning it as a novel therapeutic target for Parkinson's disease[@wang2024].
Overview
Mermaid diagram (expand to render)
SYNGR3 is a member of the synaptogyrin family of synaptic vesicle proteins. While SYNGR1 (synaptogyrin-1) has been more extensively studied, SYNGR3 has emerged as a significant player in neurodegeneration through its direct interaction with alpha-synuclein["@wang2024"]. The protein is expressed in presynaptic terminals and is involved in synaptic vesicle organization and function["@hubler2004"][@takamori2006].
Molecular Function
SYNGR3 contributes to synaptic biology through several mechanisms:
Synaptic vesicle organization: Like other synaptogyrin family members, SYNGR3 is an integral membrane protein of synaptic vesicles that participates in vesicle biogenesis and organization[@hubler2004][@takamori2006].
Presynaptic signaling: SYNGR3 interacts with other presynaptic proteins to modulate neurotransmitter release and synaptic plasticity.
Protein interaction hub: SYNGR3 directly binds to alpha-synuclein, positioning it at the intersection of synaptic function and protein aggregation pathology[@wang2024].Role in Parkinson's Disease
Alpha-Synuclein Aggregation
The groundbreaking discovery from PMID:41877387 demonstrates that SYNGR3 plays a critical role in accelerating alpha-synuclein aggregation:
- Direct interaction: SYNGR3 directly binds to the central region of alpha-synuclein
- Aggregation acceleration: SYNGR3 significantly accelerates alpha-synuclein fibril formation
- Fibril stability: SYNGR3-promoted aggregates are more resistant to proteinase K digestion, indicating more stable pathological inclusions
- Mechanism: The interaction promotes the conversion of soluble alpha-synuclein into insoluble fibrils that characterize Lewy bodies in Parkinson's disease[@bendor2013][@bridi2018]
Pathological Consequences
Overexpression of SYNGR3 in models leads to:
- Synaptic protein loss: Decreased levels of presynaptic proteins
- Mitochondrial dysfunction: Impaired mitochondrial health and energy metabolism
- Apoptosis: Increased neuronal cell death
- Motor behavioral deficits: Impaired motor function in animal models
Therapeutic Potential
The findings from this study establish SYNGR3 as a key contributor to Parkinson's disease pathogenesis. The authors highlight that SYNGR3 represents "a novel and critical promoter of alpha-synuclein aggregation and neurotoxicity" and its potential as a therapeutic target for intervention[@wang2024].
Therapeutic strategies targeting SYNGR3 include:
- SYNGR3 knockdown: Reduces alpha-synuclein aggregation and alleviates pathological and behavioral impairments
- Blocking interaction: Small molecules that disrupt the SYNGR3-alpha-synuclein interaction
- Gene therapy: Reducing SYNGR3 expression in vulnerable neurons
Relationship to SYNGR1 and the Synaptogyrin Family
SYNGR3 belongs to the synaptogyrin family alongside [SYNGR1](/genes/syngr1) (synaptogyrin-1). While both proteins are involved in synaptic vesicle function:
- SYNGR1: More widely studied, involved in vesicle pool organization and neurotransmitter release efficiency
- SYNGR3: Recently discovered role in alpha-synuclein aggregation, making it uniquely relevant to Parkinson's disease
The synaptogyrin family represents an important link between normal synaptic function and neurodegeneration, with SYNGR3 emerging as a particularly important target in alpha-synucleinopathies.
Research Context
This discovery adds to the growing understanding of how synaptic proteins contribute to neurodegenerative diseases. Unlike some rare genetic forms of Parkinson's disease, SYNGR3 variants appear to influence disease risk through its protein-protein interaction with alpha-synuclein rather than through Mendelian inheritance.
See Also
- [SYNGR1 Gene](/genes/syngr1) - Synaptogyrin-1, related family member
- [Alpha-Synuclein](/proteins/alpha-synuclein) - The protein whose aggregation is promoted by SYNGR3
- [Parkinson's Disease](/diseases/parkinsons-disease) - The disease in which SYNGR3 plays a pathogenic role
- [Synaptic Vesicle Trafficking](/mechanisms/synaptic-vesicle-trafficking) - Pathway involving SYNGR3
- [Protein Aggregation](/mechanisms/protein-aggregation) - The process accelerated by SYNGR3
- [Alpha-Synucleinopathy](/mechanisms/alpha-synuclein-pathology) - Disease mechanism overview
- [Lewy Body Dementia](/diseases/lewy-body-dementia) - Related alpha-synucleinopathy disorder
References
[Wang et al., SYNGR3 promotes alpha-synuclein aggregation and neurodegeneration in Parkinson's disease (2024)](https://pubmed.ncbi.nlm.nih.gov/41877387/) - Primary reference for SYNGR3-alpha-synuclein mechanism
[Hubler et al., Differential expression of synaptogyrins and synaptophysin (2004)](https://pubmed.ncbi.nlm.nih.gov/15126693/) - Synaptogyrin family expression
[Takamori et al., Molecular anatomy of a trafficking organelle (2006)](https://pubmed.ncbi.nlm.nih.gov/16738565/) - Synaptic vesicle protein biology
[Bendor et al., The function of alpha-synuclein (2013)](https://pubmed.ncbi.nlm.nih.gov/25887616/) - Alpha-synuclein function review
[Bridi & Hirth, Mechanisms of alpha-synuclein induced synaptopathy (2018)](https://pubmed.ncbi.nlm.nih.gov/29054301/) - Alpha-synuclein pathology mechanismsPathway Diagram
The following diagram shows the key molecular relationships involving SYNGR3 Gene discovered through SciDEX knowledge graph analysis:
Mermaid diagram (expand to render)