Biomedical Engineering Reference
In-Depth Information
patients suffering from certain psychiatric conditions, although those studies need
to be confirmed by the analysis of a higher number of individuals. Preliminary data
suggest that mutations in
SCN8A
may result in motor and cognitive deficits of
variable expressivity and that
SCN8A
may be a potential susceptibility gene for
bipolar disorder [
80
,
81
]. Results from a recent study, carried on with subjects
suffering from Dravet syndrome, a severe form of epilepsy often caused by
mutations of
SCN1A
gene, are consistent with the hypothesis that
SCN1A
mutations
can be responsible not only for epilepsy, but also for early and progressive severe
mental impairment [
82
].
2.4.8 Cancer
Over the past decade, VGSCs have been reported to be involved in various types of
cancer, such as breast cancer, prostate cancer, small and nonsmall cell lung cancer,
lymphoma, mesothelioma, neuroblastoma, and cervical cancer [
83
,
84
]. In particu-
lar, remarkable functional expression of VGSCs has been found in cancer cells with
strong metastatic potential. For instance, Na
v
1.5 subunit is highly expressed in
human metastatic breast cancer cells [
85
]. The activity of that subunit is thought to
enhance tumor invasiveness due to increased cysteine cathepsin activity [
86
]. A
different VGSC subunit, Na
v
1.7, is highly expressed in prostatic cancer, where it
contributes to the metastatic cascade by potentiating cell migration [
87
,
88
]. The
functional expression of VGSCs might be an integral component of the metastatic
process in both human small and nonsmall lung cancer cells, probably through their
involvement in the regulation of intracellular sodium homeostasis [
89
,
90
]. In
summary, VGSCs could serve in cancer research both as novel markers of the
metastatic phenotype and as potential new therapeutic targets.
3 Advances in the Development of Sodium Channel Blockers:
A Few Introductory Lines
Many of the most common neurological disorders, such as epilepsy, migraine,
neurodegeneration, and chronic pain, involve abnormalities in neuronal
excitability. VGSCs play a fundamental role in originating the rising phase of cell
membrane action potential and many experimental data indicate that the functional
VGSCs could be implicated in the pathogenesis and/or the progression of such
disorders. VGSC-interfering drugs have been used for decades to treat epileptic
seizures, the most common disease related to abnormal neuronal excitability, and it
has become evident that VGSC blockers could also be beneficial in the therapy of a
broad range of disorders.
