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Replies to post #372216 on Anavex Life Sciences Corp (AVXL)
08/31/22 1:40 PM
09/01/22 11:41 AM
A critical element of the long-term consequence of the regulation of synaptic signaling at the cellular level is probably that of transcriptional regulation. In addition to influencing neurotransmitter release, a role for nAChRs in the regulation of cell signaling and gene expression has been reported52. In neuroblastoma cells, exposure to nicotine influences the expression of a diverse set of genes, including transcription and protein-processing factors, and proteins associated with RNA binding and the plasma membrane53. For nAChRs, such transcriptional control is usually triggered by calcium influx directly through the receptors, indirectly through VDCCs, and through release from internal stores4, 54, 55, 56, 57, 58.
Regulation of neurotransmitter release The activation of nAChRs can influence gene expression for immediate early genes and genes involved in transmitter synthesis15, 52, 59, 60. In the chick ciliary ganglion61, the nAChR-mediated control of transcription relies on calcium influx and calcium release from internal stores to activate first CaMKII/IV, and then ERK/MAPK. These enzymes activate the transcription factor CREB (the cAMP response element-binding protein), which can alter gene expression.
Supplementary Figure 4: Exceptional therapeutic response
Longitudinal change in MMSE and ADCS-ADL over 148 weeks of combined studies of two patients (a and b) having SIGMAR1 gene wild type, mean high concentration levels of ANAVEX2-73 in plasma in Part B and baseline MMSE ≥20. All n=6 subjects, including patients a and b, with these response characteristics are shown in Figure 3.
An additional ten patients had “unexpected positive benefit” described by their investigator in the CRF data e.g. improved mood, increase attention, improved sleep. Eight of these patients recorded a high ANAVEX2-73 plasma concentration (≥4.0ng/ml) in Part B.
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