Synaptic dysfunction is one of the most important markers of neurodegenerative diseases, which contribute to cognitive decline and the loss of neurons. Synaptosomal-associated protein 25 (SNAP-25) is a member of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex, which plays a significant role in the exocytosis of synaptic vesicles and the release of neurotransmitters. Recent studies have shown that expression levels of SNAP-25 are altered in various neurodegenerative disorders, including Alzheimer's disease (AD), Huntington's disease (HD), and Creutzfeldt-Jakob disease (CJD). These investigations led to the consideration of SNAP-25 as a potential biomarker of synaptic degeneration. Understanding the role of SNAP-25 in neurodegeneration will aid in early diagnosis, disease monitoring, and therapeutic development, and will also provide new insights into synaptic dysfunction as a main feature of neurodegenerative diseases. Therefore, this paper explores the physiological role of SNAP-25, its involvement in synaptic pathology, and the implications of its dysregulation in neurodegenerative conditions, such as AD, HD, and CJD. Literature regarding cerebrospinal fluid (CSF) SNAP-25 levels as a diagnostic marker were reviewed and its applications in detecting the progression of the disease have been discussed. Additionally, the limitations of SNAP-25 as a biomarker, including variability across studies and the need for further validation have been addressed.
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http://dx.doi.org/10.1016/j.cca.2025.120236 | DOI Listing |
Clin Chim Acta
March 2025
Shahid Beheshti University of Medical Sciences, Tehran, Iran. Electronic address:
Synaptic dysfunction is one of the most important markers of neurodegenerative diseases, which contribute to cognitive decline and the loss of neurons. Synaptosomal-associated protein 25 (SNAP-25) is a member of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex, which plays a significant role in the exocytosis of synaptic vesicles and the release of neurotransmitters. Recent studies have shown that expression levels of SNAP-25 are altered in various neurodegenerative disorders, including Alzheimer's disease (AD), Huntington's disease (HD), and Creutzfeldt-Jakob disease (CJD).
View Article and Find Full Text PDFJ Neural Transm (Vienna)
March 2025
Egas Moniz Center for Interdisciplinary Research (CiiEM), Egas Moniz School of Health & Science, Campus Universitário, Quinta da Granja, 2829-511, Caparica, Almada, Portugal.
Botulinum toxin type A (BoNT) has emerged as a potential alternative to conventional therapies to many debilitating chronic diseases characterised by inflammatory states. However, the biological rationale remains ambiguous. Our review aimed to systematically assessed which biochemical biomarkers have been reported in clinical research to evaluate BoNT analgesic and mood-lifting effects in head and neck chronic conditions related to inflammation.
View Article and Find Full Text PDFAlzheimers Res Ther
February 2025
Sant Pau Memory Unit, Institut de Recerca Sant Pau, Universitat Autonoma de Barcelona, c/Sant Quintí 77, Barcelona, 08041, Spain.
Background: Synaptic protein levels in cerebrospinal fluid (CSF) may represent much-needed objective biomarkers of cognitive impairment, disease progression and drug efficacy in patients with dementia with Lewy bodies (DLB). Soluble N-ethylmaleimide-sensitive factor attachment proteins receptors (SNARE) proteins, such as VAMP-2 and SNAP-25, are implicated in α-synuclein pathophysiology and CSF levels of these proteins are associated with pathophysiological biomarkers and cognitive decline in Alzheimer's disease (AD). The aim of the study was to compare CSF levels of VAMP-2 and SNAP-25 in patients with DLB to cognitively unimpaired controls and AD patients and study their association with cognitive performance and AD and neurodegeneration biomarkers.
View Article and Find Full Text PDFUnlabelled: Neurotransmitter release is triggered by the fusion of synaptic vesicles with the plasma membrane, orchestrated by SNARE proteins Synaptobrevin 2 (Syb2), Syntaxin 1A (Stx1A), and SNAP25. Recent experimental studies showed that Stx1A palmitoylation of C271/C272 promotes spontaneous neurotransmitter release. However, the mechanistic role of SNARE transmembrane domain (TMD) palmitoylation in membrane fusion remains unclear.
View Article and Find Full Text PDFBiophys J
February 2025
Department of Cell Biology & Physiology, Brigham Young University, Provo, Utah; Neuroscience Center, Brigham Young University, Provo, Utah. Electronic address:
SNAP-25, together with other SNARE proteins, drives fusion of synaptic vesicles with the nerve cell membrane, leading to neurotransmitter release. It is unique in contributing two α helices to the four-helix bundle known as the SNARE complex. Complex formation drives fusion as these proteins transform from a disordered to ordered (coiled-coil) state.
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