TRH (
thyroliberin) and its analogues were reported to possess
neuroprotective effects in cellular and animal experimental models of acute and chronic
neurodegenerative diseases. In the present study we evaluated effects of TRH and its three stable analogues,
montirelin (CG-3703),
RGH-2202 and Z-TRH (N-(carbobenzyloxy)-pGlutamyl-Histydyl-
Proline) on the neuronally differentiated human
neuroblastoma SH-SY5Y cell line, which is widely accepted for studying potential
neuroprotectants. We found that TRH and all the tested analogues at concentrations 0.1-50 μM attenuated cell damage induced by MPP(+) (2 mM),
3-nitropropionate (10 mM),
hydrogen peroxide (0.5 mM),
homocysteine (250 μM) and
beta-amyloid (20μM) in
retinoic acid differentiated SH-SY5Y cells. Furthermore, we demonstrated that TRH and its analogues decreased the
staurosporine (0.5 μM)-induced LDH release,
caspase-3 activity and DNA fragmentation, which indicate the anti-apoptotic proprieties of these
peptides. The
neuroprotective effects of TRH (10 μM) and
RGH-2202 (10 μM) on St-induced cell death was attenuated by inhibitors of PI3-K pathway (
wortmannin and
LY294002), but not MAPK/ERK1/2 (
PD98059 and
U0126). Moreover, TRH and its analogues at neuroprotective concentrations (1 and 10 μM) increased expression of Bcl-2
protein, as confirmed by Western blot analysis. All in all, these results extend data on neuroprotective properties of TRH and its analogues and provide evidence that mechanism of anti-apoptotic effects of these
peptides in SH-SY5Y cell line involves induction of PI3K/Akt pathway and Bcl-2. Furthermore, the data obtained on human cell line with a dopaminergic phenotype suggest potential utility of TRH and its analogues in the treatment of some
neurodegenerative diseases including
Parkinson's disease.