Disease relevance of SYP

• The data suggest that CaN and MAP2, together with SYP, can be useful tools for identifying and characterizing of the central neurocytoma [1].
• We studied synaptophysin immunohistochemical expression in 35 human liver specimens (normal and different pathological conditions), in rat models of galactosamine hepatitis and carbon tetrachloride-induced cirrhosis, and in freshly isolated rat stellate cells [2].
• In a frozen chronic hepatitis case (with expected activated hepatic MF and HSC), HSC were negative to synaptophysin, GFAP and NCAM [3].
• Although synaptophysin has been implicated in neurotransmitter release, and decreased synaptophysin levels have been associated with several neurodegenerative diseases, the molecular mechanism that regulates the degradation of synaptophysin remains unsolved [4].
• Surface perikaryal labeling for SYN is not restricted to the neoplastic neurons of ganglion cell tumors and should be cautiously interpreted, particularly when neurosurgical material derives from the spinal cord [5].

Psychiatry related information on SYP

• In contrast to patients with schizophrenia, GAP-43 and synaptophysin levels in subjects with bipolar disorder did not differ from controls [6].
• Synaptic pathology in the anterior cingulate cortex in schizophrenia and mood disorders. A review and a Western blot study of synaptophysin, GAP-43 and the complexins [7].
• Expression of MAP2 does not seem to indicate difficulty of task or duration of training time, whereas increases in synaptophysin expression, which appear diffusely across the cortex, seem to be correlated with the first 5 days of motor skill learning [8].
• APP with Kunitz type protease inhibitor domain (KPI) correlates with neuritic plaque density but not with cortical synaptophysin immunoreactivity in Alzheimer's disease and non-demented aged subjects: a multifactorial analysis [9].
• This immunohistochemical study compares the expression of synaptophysin (SYP) in the striatum in Huntington's disease (HD) with that of calcineurin (CaN), a marker for striatal medium-sized spinous neurons [10].

High impact information on SYP

• Topogenesis and sorting of synaptophysin: synthesis of a synaptic vesicle protein from a gene transfected into nonneuroendocrine cells [11].
• Diverse nonneuroendocrine (non-NE) cells were forced to express synaptophysin (SY), the major and typical transmembrane glycoprotein of small (30-80 nm) neurotransmitter vesicles of NE cells, using microinjection of RNA synthesized in vitro from cDNA or transient and stable transfections with cDNA brought under SV40 promoter control [11].
• The glycoprotein synthesized in non-NE cells is indistinguishable from SY of NE cells and is integrated with similar, if not identical, orientation in the membranes of a specific, novel type of small cytoplasmic vesicle that structurally resembles synaptic vesicles and in which SY is the only major protein detected [11].
• Identification and localization of synaptophysin, an integral membrane glycoprotein of Mr 38,000 characteristic of presynaptic vesicles [12].
• This protein, for which we propose the name synaptophysin*, provides a molecular marker for the presynaptic vesicle membrane and may be involved in synaptic vesicle formation and exocytosis [12].

Chemical compound and disease context of SYP

• Surface perikaryal labeling on immunohistochemical assay for synaptophysin (SYN)--a glycoprotein component of synaptic vesicle membranes--has been posited to distinguish the neoplastic neuronal elements of gangliogliomas from native central nervous system neurons overrun by gliomas invasive of gray matter [5].
• Continuous estradiol replacement over two months loses effect on apoE, LRP, and synaptophysin and suppresses reactive gliosis [13].
• A comparison of synaptophysin, chromogranin, and L-dopa decarboxylase as markers for neuroendocrine differentiation in lung cancer cell lines [14].
• Immunohistochemical markers such as chromogranin A, synaptophysin, and serotonin have proven to be useful diagnostic tools in evaluating carcinoid tumors [15].
• Snap-frozen samples from 22 primitive neuroectodermal tumors (PNETs) primary in the central nervous system were studied with antibodies to synaptophysin, bombesin, somatostatin, substance P, vasoactive intestinal polypeptide, all classes of intermediate filaments, and desmoplakins I and II [16].

Biological context of SYP

• Preliminary analysis of the latter suggested that this might reflect a high density of coding sequences and we therefore undertook the complete sequencing of a SYP-containing cosmid [17].
• This revealed the presence of 29 putative exons, organized into three genes, in addition to the 7 exons of the complete SYP coding region, all mapping within a 44-kb interval [17].
• The region has an elevated GC content (>53%), and we identified CpG islands associated with the 5' ends of SYP, A4, and LMO6 [17].
• Synaptophysin is a protein involved in neurotransmitter exocytosis and is a neuroendocrine marker [2].
• Here, we show that inhibition of histone deacetylase activity in P19 cells is sufficient to activate transcription of the synaptophysin and synapsin I genes, indicating that neuronal differentiation and impairment of histone deacetylases results in a similar gene expression pattern [18].

Anatomical context of SYP

• Finally, electron microscopy showed the presence of small electron translucent vesicles, comparable to the synaptophysin-reactive synaptic vesicles in neurons, in stellate cell projections [2].
• Synaptophysin and GAP-43 mRNA levels in the hippocampus of subjects with schizophrenia [19].
• Synaptophysin and growth associated protein-43 (GAP-43) are synaptic proteins colocalized to the presynaptic terminal, and involved in regulating transmitter release and synaptic plasticity [19].
• Immunostaining of SYN in the cerebral cortex (an area not exhibiting spongiform lesions) was similar in viral infected and age-matched control mice [20].
• Using in situ hybridization, we investigated the levels of synaptophysin and GAP-43 mRNA in the medial temporal lobe of 10 normal subjects, 11 subjects with schizophrenia and 10 psychiatric control subjects [19].

Associations of SYP with chemical compounds

• Cholesterol binds to synaptophysin and is required for biogenesis of synaptic vesicles [21].
• To assess the validity of this criterion in the evaluation of intramedullary neoplasms, we screened formalin-fixed, paraffin-embedded sections from 35 histologically unremarkable spinal cords (removed at autopsy) using commercially available monoclonal antibodies to SYN [5].
• Upon appropriate induction, 100% of 1C11 precursor cells develop neurite extensions and acquire neuronal markers (N-CAM, synaptophysin, gammagamma-enolase, and neurofilament) as well as the general functions of either serotonergic (1C11*(/5HT)) (5HT, 5-hydroxytryptamine) or noradrenergic (1C11**(/NE)) (NE, norepinephrine) neurons [22].
• During inflammation, angiotensin II expression was elevated, STAT3 was activated, and synaptophysin and rhodopsin expression were reduced [23].
• The effects of betamethasone on neuronal development and function were determined in the fetal baboon brain by examination of cytoskeletal microtubule associated proteins (MAPs) and the presynaptic marker protein synaptophysin [24].

Physical interactions of SYP

• Thus, TNF produced by activated glial cells in inflammatory or degenerative neurological diseases acts on neurites by acting on the kinesin-tubulin complex and inhibits axonal mitochondria and synaptophysin transport via JNK [25].
• Insertion of synaptophysin in the first three arm repeats selectively inactivates plakoglobin binding to desmoglein and desmocollin [26].
• We conclude that the dynamin/synaptophysin complex functions in a clathrin-independent mechanism of SV endocytosis that is required for efficient synaptic transmission [27].
• This investigation concerns the expression of paired helical filaments, tau protein, ubiquitin, beta-amyloid protein, and synaptophysin in the hippocampus of patients with parkinsonism-dementia complex on Guam (PDC) and Alzheimer's disease [28].

Co-localisations of SYP

• In cells treated with nerve growth factor, hVAChT immunoreactivity alone co-localized with synaptophysin and was abundantly expressed on synaptic vesicle clusters [29].

Regulatory relationships of SYP

• Synaptophysin was expressed in 57% of synaptoporin-containing small dorsal root ganglion neurons and in large dorsal root ganglion neurons [30].
• Furthermore, TNF inhibited axonal transport of mitochondria and synaptophysin by reducing the mobile fraction via JNK [25].
• Neuron-specific enolase was expressed with SYP in most adenomas, whereas chromogranin was present only in a few tumors [31].
• In cell lines deficient in both Brm and BRG1, exogenous Brm or BRG1 suppressed expression of these neuronal genes in an ATP-dependent manner and induced efficient and specific deacetylation of histone H4 around the NRSF binding site present in the synaptophysin gene by a large complex containing the recruited functional SWI/SNF complex [32].
• These comprised a patterned biphasic mixture of sheets of synaptophysin-expressing small round cells and pseudorosettes of GFAP-positive rudimentary astrocytes along vascular cores [33].

Other interactions of SYP

• These neuronal precursors expressed betaIII tubulin, the dendritic marker MAP2 and the presynaptic marker synaptophysin after 7 days of in vitro maturation [34].
• In this study, we compared the expression of AP180 with synaptophysin in the aged human brain using confocal immunofluorescence microscopy [35].
• Cellular expression and specific intragranular localization of chromogranin A, chromogranin B, and synaptophysin during ontogeny of pancreatic islet cells: an ultrastructural study [36].
• It was found that during prenatal development both AKAP79 and SYN expression increased gradually although a major alteration in the distribution of the proteins within the two compartments of the red nucleus was not observed [37].
• Four glands that were strongly and diffusely positive for CT were CgB and SYN negative [38].

Analytical, diagnostic and therapeutic context of SYP

• Double staining for alpha-smooth muscle actin and synaptophysin, detected by confocal laser scanning microscopy, unequivocally demonstrated colocalization of both markers in lobular stellate cells [2].
• Synaptophysin mRNA levels were significantly reduced in several hippocampal subfields in both the schizophrenic and psychiatric control groups [19].
• We investigated human thymic tissue by immunohistochemistry and in situ hybridization for the presence of synaptophysin-producing cells [39].
• Colocalisation of synaptophysin has been studied in different neuroendocrine cell types in histologically normal mucosa from human gastrointestinal tract (corpus, antrum, duodenum, ileum and colon) using double-immunofluorescence stainings [40].
• Immunoblotting analysis of the SNARE proteins revealed selective reduction of the levels of synaptobrevin and synaptophysin in synaptosomes from stg cerebellum [41].

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