The galanin receptor 2/3 agonist Gal2-11 protects the SN56 cells against beta-amyloid 25-35 toxicity.
The neuropeptide galanin is a modulator of cholinergic function and may play a role in A beta peptide-induced degeneration of cholinergic forebrain neurons. We have studied the effect of galanin and its galanin receptor subtype 2/3 agonist Gal2-11on toxicity induced by freshly-prepared beta-amyloid(25-35) in the cholinergic cell line SN56. Both nuclear fragmentation and caspase-3 expression were analysed. beta-amyloid(25-35)-exposure induced a significant increase in caspase-3 mRNA expression after 30, 60, 90 or 150 min of beta-amyloid(25-35) exposure. These effects were abolished in the presence of Gal2-11 (10 nM). Similarly, beta-amyloid(25-35)-induced nuclear fragmentation was prevented by the galanin agonist at all time points studied. These findings indicate that the galanin 2/3 agonist Gal2-11 protects SN56 cholinergic cells from beta-amyloid(25-35)-induced cell death and that this action is mediated by an early reduction of caspase-3 expression.
Pirondi
S
S
DIMORFIPA, University of Bologna, Bologna, Italy.
Giuliani
A
A
Del Vecchio
G
G
Giardino
L
L
Hökfelt
T
T
Calzà
L
L
D000109:Acetylcholine / Q000378:metabolism; D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000633:toxicity; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D020532:Basal Nucleus of Meynert / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D053148:Caspase 3 / Q000235:genetics; D002461:Cell Line, Transformed; D002799:Cholinergic Fibers / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D053938:DNA Fragmentation / Q000187:drug effects; D019004:Galanin / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D009410:Nerve Degeneration / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D010446:Peptide Fragments / Q000037:antagonists & inhibitors* / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D044092:Receptor, Galanin, Type 2 / Q000819:agonists* / Q000378:metabolism; D013997:Time Factors
D016229:Amyloid beta-Peptides; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D012333:RNA, Messenger; D044092:Receptor, Galanin, Type 2; C074636:amyloid beta-protein (25-35); C434734:galanin (2-11)-amide; D019004:Galanin; D053148:Caspase 3; D000109:Acetylcholine