Association of Alpha-Soluble NSF Attachment Protein with Epileptic Seizure

Abstract

Alpha-soluble N-ethylmaleimide-sensitive factor (NSF) attachment protein (αSNAP) is a ubiquitous and indispensable component of membrane fusion machinery. There is accumulating evidence that mild alterations of αSNAP expression may be associated with specific pathological conditions in several neurological disorders. This study aimed to assess αSNAP expression in temporal lobe epilepsy (TLE) patients and pilocarpine-induced rat model and to determine whether altered αSNAP expression leads to increased susceptibility to seizures. The expression of αSNAP was assessed in the temporal lobe from patients with TLE and pilocarpine-induced epileptic rats. In addition, αSNAP expression was silenced by lentivirus pLKD-CMV-GFP-U6-NAPA (primer: GGAAGCATGCGAGATCTATGC) in animals. At day 7, the animals were kindled by pilocarpine and then the time of latency to seizure and the incidence of chronic idiopathic epilepsy seizures were assessed. The immunoreactivity to alpha-SNAP was utilized to measure expression of this protein in the animal. By immunohistochemistry, immunofluorescence, and western blotting, we found significantly lower αSNAP levels in patients with TLE. αSNAP expression showed no obvious change in pilocarpine-induced epileptic rats, from 6 h to 3 days after seizure, compared with the control group, in the acute stage; however, αSNAP levels were significantly lower in the chronic phase (day 7, months 1 and 2) in epileptic rats. Importantly, behavioral data revealed that αSNAP-small interfering RNA (siRNA) could decrease the time of latency to seizure and increase the incidence of chronic idiopathic epilepsy seizures compared with the control group. αSNAP is mainly expressed in the neuron brain tissue of patients with TLE and epileptic animals. Our findings suggest that decreasing αSNAP levels may increase epilepsy susceptibility, providing a new strategy for the treatment of this disease.

Comparative analysis of hippocampal extracellular space uncovers widely altered peptidome upon epileptic seizure in urethane-anaesthetized rats

“…These peptides were upregulated upon 4-AP treatment. Napa was downregulated in patients with TLE and pilocarpine-induced seizures 7 days post-treatment, and no changes were found in the acute phase (from 6 h and 3 days) [ 79 ]. However, kainate-induced status epilepticus increased the number of docked synaptic vesicles 7 days post-treatment [ 11 ].…”

Bioinformatics and next generation sequencing data analysis to identify key genes and pathways influencing in Parkinson’s disease

“…The expression and prognosis of TUBB2A [399], PAK1 [400], PRKCG (protein kinase C gamma) [401], CACNA1G [402], ATP1A3 [403] and KCNJ10 [404] have been investigated in ataxia. SCN3B [405], PCDH19 [406], CNTNAP2 [407], STXBP1 [408], CHRNB2 [409], NAPA (NSF attachment protein alpha) [410], STX1B [411], GABRG2 [412], CAMKK2 [144], CNTNAP2 [413], ARHGEF9 [414], COX8A [415], CALHM1 [416], SLC45A1 [417], TLR5 [418] and KCNJ10 [419] could be acuseful prognostic biomarker in epilepsy. The altered expression of NPTX2 [420], VAMP2 [421], PRKAR1B [422], SNCB (synuclein beta) [199], AP2M1 [423], TUBA4A [424], KIF17 [425] and SYK (spleen associated tyrosine kinase) [426] might be related to the progression of dementia.…”

The disease-specific proteins in striatum of the mouse models of Parkinson's disease induced by rotenone and MPTP

“…Furthermore, α-SNAP was found to interact with agnoprotein to modulate exocytosis in the study of human polyomavirus BK [35]. Alteration of α-SNAP may be related to central nervous system diseases [36]. Reduced expression of α-SNAP was reported in Down's syndrome, temporal lobe epilepsy (TLE) and Creutzfeldt-Jakob disease (CJD); however, increased α-SNAP expression was reported in Huntington's disease.…”