In:
CNS Neuroscience & Therapeutics, Wiley, Vol. 19, No. 10 ( 2013-10), p. 764-772
Abstract:
Neuronal loss via apoptosis in CNS is the fundamental mechanism underlying various neurodegenerative diseases. Compounds with antiapoptotic property might have therapeutic effects for these diseases. In this study, bis(propyl)‐cognitin ( B 3 C ), a novel dimer that possesses anti‐ AC h E and anti‐ N ‐methyl‐ d ‐aspartate receptor activities, was investigated for its neuroprotective effect on K + deprivation‐induced apoptosis in cerebellar granule neurons ( CGN s). Methods Cerebellar granule neurons were switched to K + deprived medium with or without B 3 C . 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium assay, fluorescein diacetate ( FDA )/propidium iodide ( PI ) staining, H oechst staining, and DNA laddering assays were applied to detect cytotoxicity and apoptosis. Additionally, the expression of p‐ VEGFR ‐2, p‐ A kt, p‐glycogen synthase kinase 3β ( GSK 3β), and p‐extracellular signal‐regulated kinase ( ERK ) was examined in CGN s. Results Switching CGN s to K + deprived medium resulted in remarkable apoptosis, which could be substantially blocked by B 3 C treatment ( IC 50 , 0.37 μM). Moreover, a rapid decrease in p‐ T yr1054‐ VEGFR ‐2 was observed after the switch. B 3 C significantly reversed the inhibition of p‐ T yr1054‐ VEGFR ‐2 as well as A kt and ERK pathways. VEGFR ‐2 inhibitor PTK 787/ ZK 222584, as well as PI 3‐ K inhibitor LY 294002 and MEK inhibitor PD 98059, each abolished the neuroprotective effect of B 3 C . Conclusions Our results demonstrate that B 3 C blocks K + deprivation‐induced apoptosis in CGN s through regulating VEGFR ‐2/ A kt/ GSK 3β and VEGFR ‐2/ ERK signaling pathways, providing a molecular insight into the therapeutic potential of B 3 C for the treatment of neurodegenerative diseases.
Type of Medium:
Online Resource
ISSN:
1755-5930
,
1755-5949
DOI:
10.1111/cns.2013.19.issue-10
Language:
English
Publisher:
Wiley
Publication Date:
2013
detail.hit.zdb_id:
2423467-9
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