Galanin protects against intracellular amyloid toxicity in human primary neurons.
Galanin and galanin receptors are upregulated in the brain regions associated with Alzheimer's disease (AD). However, the consequence of this overexpression is still unknown, particularly in human neurons. Here, we investigate the possible protective effects of galanin against intracellular amyloid-beta (Abeta)1-42 toxicity, as well as other insults including staurosporine, etoposide, hydrogen peroxide, and serum depletion in cultured human primary neurons. The results show that galanin is protective against intracellular Abeta cytotoxicity and all of the above insults at sub-nanomolar physiological concentrations. The galanin protection may be mediated by galanin receptor 2 and down-regulation of Bax level. The data from the present study provide a potential drug target for therapy or prevention of neurodegenerative diseases, including AD.
Cui
Jia
J
Laboratory of Neurobiology and State Key Laboratory of Biomembrane and Membrane Biotechnology, College of Life Sciences, Peking University, Beijing, China.
Chen
Qiuyue
Q
Yue
Xiaojing
X
Jiang
Xuejun
X
Gao
George F
GF
Yu
Long-Chuan
LC
Zhang
Yan
Y
D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000704:Analysis of Variance; D001921:Brain / Q000166:cytology; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D004347:Drug Interactions; D005047:Etoposide / Q000633:toxicity; D045604:Extracellular Fluid / Q000187:drug effects; D005333:Fetus; D019004:Galanin / Q000494:pharmacology*; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D020287:In Situ Nick-End Labeling / Q000379:methods; D008845:Microinjections / Q000379:methods; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009498:Neurotoxins / Q000633:toxicity*; D010446:Peptide Fragments / Q000633:toxicity*; D044088:Receptors, Galanin / Q000378:metabolism; D019311:Staurosporine / Q000633:toxicity; D013997:Time Factors; D014161:Transduction, Genetic / Q000379:methods; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D016229:Amyloid beta-Peptides; D016895:Culture Media, Serum-Free; D018696:Neuroprotective Agents; D009498:Neurotoxins; D010446:Peptide Fragments; D044088:Receptors, Galanin; C075222:amyloid beta-protein (1-42); D051028:bcl-2-Associated X Protein; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D005047:Etoposide; D019004:Galanin; D006861:Hydrogen Peroxide; D019311:Staurosporine