Ask about this productRelated genes to: SNAP25 antibody
- Gene:
- SNAP25 NIH gene
- Name:
- synaptosome associated protein 25
- Previous symbol:
- SNAP
- Synonyms:
- SNAP-25, RIC-4, RIC4, SEC9, bA416N4.2, dJ1068F16.2
- Chromosome:
- 20p12.2
- Locus Type:
- gene with protein product
- Date approved:
- 1995-01-24
- Date modifiied:
- 2016-10-05
Related products to: SNAP25 antibody
Related articles to: SNAP25 antibody
- Synaptic vesicle fusion is orchestrated by the soluble N-ethylmaleimide-sensitive factor attachment receptor (SNARE) complex. The SNARE complex includes SNAP25, synaptobrevin-2, and syntaxin-1. This machinery drives action potential-evoked release, as well as the majority of spontaneous release. Mutations in components of the SNARE machinery can differentially affect spontaneous or evoked release and result in severe neurodevelopmental phenotypes, as exemplified by SNAP25 encephalopathies that arise from mutations in the SNAP25 gene. Among various pathogenic SNAP25 variants, L50S, V48F, and D166Y increase spontaneous glutamate release that destabilizes network activity. Patients who carry these variants develop recurrent seizures that are refractory to conventional antiepileptic drugs, which primarily act on components of evoked neurotransmission and leave spontaneous release abnormalities unaddressed. To surmount this limitation, we explored a strategy targeting homeostatic plasticity mechanisms with lithium, which has been shown to downscale postsynaptic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPAR). In vitro, lithium corrected cellular phenotypes in neurons expressing SNAP25 variants. In vivo, we generated a knock-in mouse model recapitulating the SNAP25 L50S mutation to test these results. These mice displayed increased neonatal mortality, infertility, hypomobility, frequent seizure activity, anxiety-like behavior, social deficits, and impaired learning and memory. Chronic lithium treatment reduced seizure frequency and ameliorated long-term memory and locomotor activity. Taken together, lithium alleviated synaptic and behavioral disturbances driven by pathological spontaneous glutamate release by inducing homeostatic AMPAR downscaling. Thus, this work provides a mechanistically grounded therapeutic strategy for SNAP25 encephalopathies and other disorders characterized by elevated spontaneous glutamate release. - Source: PubMed
Publication date: 2026/08/27
Uzay BurakMa Z ZackUzay Ihsan AlpAlten BarisMonteggia Lisa MKavalali Ege T - Enterovirus A71 (EV-A71) and enterovirus D68 (EV-D68) are recognised as causative agents of severe neurological complications, including acute flaccid myelitis (AFM). However, the molecular mechanisms underlying the neurovirulence and effects on neuromuscular integrity remain poorly understood. Here, we employed human induced pluripotent stem cell-derived neuromuscular organoids (NMOs) to investigate the cellular tropism and pathogenic effects of EV-A71 and EV-D68 in a human-relevant context. Both viruses infected neuronal populations within NMOs, with EV-A71 exhibiting higher levels of viral replication than EV-D68. Transcriptomic analysis revealed downregulation of neuronal and muscular gene networks following infection. EV-A71 preferentially suppressed neuronal pathways, while both viruses exerted comparable effects on muscle-associated gene expression. These transcriptional changes highlighted alterations in pathways governing neuronal and muscle function and communication, prompting examination of synaptic vesicle machinery components. At the protein level, both viruses were associated with sporadic cleavage of the neuronal SNARE protein synaptosomal-associated protein 25 (SNAP25). In addition, infection with either virus increased cleaved caspase-3 levels, consistent with activation of apoptotic signalling. Together, these findings indicate virus-specific downstream effects and establish NMOs as a robust platform for dissecting enterovirus-host interactions relevant to AFM. - Source: PubMed
Publication date: 2026/08/04
Schotting Amber JGarcía-Rodríguez InésFreeze ElineAmbikan Anoop TWagner MichaelMioch MiraMoffelein Aymeric P Y LJackson WilliamPajkrt DasjaWolthers Katja CSá Renata Vieira deSridhar Adithya - Non-motor symptoms (NMS) in Parkinson's disease (PD) are clinically impactful and lack reliable blood-based biomarkers. Neural-derived extracellular vesicles (NDEVs) enriched from serum may reflect central neurodegenerative processes. In this cross-sectional study, we examined associations between NMS burden and NDEV-associated proteins in 68 patients with PD. NDEVs were immunocaptured from serum using an anti-L1CAM approach and characterized according to MISEV guidelines. NDEV-associated oligomeric α-synuclein, SNARE complex proteins (SNAP-25, VAMP2, STX-1A), and neurotrophic factors (BDNF, GDNF, CDNF) were quantified by ELISA and related to NMS burden and PCA-derived non-motor domains, adjusting for age, sex, disease duration, MDS-UPDRS III, and levodopa equivalent daily dose (LEDD). Higher NDEV-associated oligomeric α-synuclein correlated with total NMSS score (partial Spearman's ρ = 0.252, p = 0.02) and with hallucinations (domain 4) and attention/memory (domain 5). These associations were confirmed by multivariable regression analyses. In domain-specific models, oligomeric α-synuclein was independently associated with worse cognitive and behavioral-psychotic scores, whereas higher STX-1A and lower CDNF were associated with greater affective-motivational symptom severity. No significant associations were observed for autonomic or sleep domains. These findings support NDEV-associated oligomeric α-synuclein as a candidate biomarker of non-motor symptom burden in PD and warrant longitudinal validation. - Source: PubMed
Publication date: 2026/07/28
Meloni MarioAgliardi CristinaSalvatore AnnaSaibene Francesca LeaMarano MassimoCastagna AnnaArcuri PietroZanzottera MilenaGuerini Franca RosaClerici Mario - Botulinum neurotoxin serotypes A and E (BoNT/A and BoNT/E) cleave SNAP25 and are widely used in therapeutic applications. Redirecting the substrate specificity of their protease domains, LC/A and LC/E, could expand their utility to new therapeutic targets. Here, we report a comparative protein engineering strategy that integrates prior mutagenesis, bioinformatics, and structural insights to reprogram LC protease specificity. Directed evolution yielded a 14-mutation LC/A variant with 273-fold greater specificity for SNAP23 than a previously reported engineered protease. Insights from LC/A engineering then guided six rounds of directed evolution to generate an 8-mutation LC/E variant with a 26,000-fold increase in SNAP29 cleavage and no detectable activity toward SNAP25. Importantly, both engineered proteases retain their altered substrate preferences under physiologically relevant substrate and salt concentrations. Together, these findings establish comparative protein engineering as an effective framework for retargeting botulinum neurotoxin proteases. - Source: PubMed
Publication date: 2026/08/26
Garrido Jason ESalcedo Gabriela SStrul Max WAshby Shareen NPamidi Arjun SCho JaehoWaldvogel Katherine GWiriadinata Elizabeth LNedic TeodoraKaewtatip NatnichaKato HonokaChan MayaDyer Rebekah PWeiss Gregory A - Schwann cells (SC) myelinate peripheral axons and orchestrate nerve regeneration after injury by switching between myelinating, proliferative and repair states. Evidence suggests that Botulinum Neurotoxin Type A (BoNT/A) influences SC biology, potentially supporting nerve repair and pain relief in peripheral neuropathic pain (PNP) models. However, BoNT/A receptor and target expression in human SC (hSC) remains poorly explored. Here, this translational gap was addressed by transcriptionally profiling genes encoding BoNT/A-relevant receptors and targets in primary hSC and testing whether paclitaxel evokes hSC phenotype plasticity in vitro based on changes in gene expression. Primary hSC were isolated, cultured, and treated with paclitaxel or vehicle, followed by RT-qPCR profiling of hSC markers and BoNT/A receptor/targets genes. Untreated hSC expressed moderate and , with low levels, suggesting a non-myelinating state profile. Transcripts encoding the BoNT/A receptor machinery (SV2A, SYT1) and the target SNAP25 were detectable at moderate levels. Paclitaxel induced changes in gene expression: and decreased (up to two-fold), whereas and increased, accompanied by reduced , indicating a shift toward a more differentiated transcriptional state. These data indicate hSC transcriptional plasticity in vitro and provide transcriptional evidence for the expression of BoNT/A-related molecular components in non-neuronal human cells. - Source: PubMed
Publication date: 2026/07/24
Sánchez-Carranza OscarJatzke ClaudiaGravius AndreasNagel Jens