The hyperforin derivative IDN5706 occludes spatial memory impairments and neuropathological changes in a double transgenic Alzheimer's mouse model.
The use of natural compounds is an interesting stratagem in the search of drugs with therapeutic potential for the treatment of Alzheimer's disease (AD). We report here the effect of the hyperforin derivative (IDN5706, tetrahydrohyperforin), a semi-synthetic derivative of the St. John's Wort, on the brain neuropathology, learning and memory in a double transgenic (APPswe, PS-1dE9) mouse model of AD. Results indicate that, IDN5706 alleviates memory decline induced by amyloid-beta (Abeta) deposits as indicated by the Morris water maze paradigm. Moreover, the analysis of Abeta deposits by immunodetection and thioflavin-S staining of brain sections, only reveals a decrease in the frequency of the larger-size Abeta deposits, suggesting that IDN5706 affected the turnover of amyloid plaques. Immunohistochemical analysis, using GFAP and n-Tyrosine indicated that the hyperforin derivative prevents the inflammatory astrocytic reaction and the oxidative damage triggered by high Abeta deposit levels. We conclude that the hyperforin derivative, IDN5706, has therapeutic potential for prevention and treatment of AD.
Cerpa
W
W
Centro de Envejecimiento y Regeneración, Departamento de Biología Celular y Molecular, Pontificia Universidad Católica de Chile, Santiago, Chile.
Hancke
J L
JL
Morazzoni
P
P
Bombardelli
E
E
Riva
Antonella
A
Marin
P P
PP
Inestrosa
Nibaldo C
NC
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000473:pathology; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D001643:Bridged Bicyclo Compounds / Q000494:pharmacology / Q000627:therapeutic use; D004195:Disease Models, Animal; D004660:Encephalitis / Q000188:drug therapy / Q000503:physiopathology / Q000517:prevention & control; D005904:Glial Fibrillary Acidic Protein / Q000032:analysis / Q000378:metabolism; D005911:Gliosis / Q000188:drug therapy / Q000503:physiopathology / Q000517:prevention & control; D006801:Humans; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008569:Memory Disorders / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D051379:Mice; D008822:Mice, Transgenic; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D010696:Phloroglucinol / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D013729:Terpenes / Q000494:pharmacology* / Q000627:therapeutic use; D014443:Tyrosine / Q000032:analysis / Q000378:metabolism
D016229:Amyloid beta-Peptides; D001643:Bridged Bicyclo Compounds; D005904:Glial Fibrillary Acidic Protein; D013729:Terpenes; D014443:Tyrosine; D010696:Phloroglucinol; C001654:hyperforin