Caprospinol reduces amyloid deposits and improves cognitive function in a rat model of Alzheimer's disease.
Alzheimer's disease (AD), the most prominent form of dementia in elderly, is a yet incurable degenerative neurological illness characterized by memory loss. Here, we used an AD rat model to investigate the in vivo efficacy of caprospinol, a disease-modifying steroid developed on the concept that reduced synthesis of 22R-hydroxycholesterol in the AD brain increases beta-amyloid neurotoxicity. Caprospinol treatment of diseased rats attenuated memory impairment, as assessed using Morris watermaze tests. This recovery of cognitive function was accompanied by a reduction in hippocampal amyloid deposits, astrogliosis, neurodegeneration and Tau protein phopshorylation. In parallel studies, caprospinol bioavailability in normal rat forebrain was found to be dependent on the dose and duration of the treatment, demonstrating the ability of the compound to cross the blood-brain barrier. These results position caprospinol as a promising drug candidate for AD treatment.
Lecanu
L
L
The Research Institute of the McGill University Health Centre, Department of Medicine, McGill University, Montreal, QC, Canada.
Rammouz
G
G
McCourty
A
A
Sidahmed
E K
EK
Greeson
J
J
Papadopoulos
V
V
D000544:Alzheimer Disease / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000473:pathology; D002208:Caproates; D003072:Cognition Disorders / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D004144:Diosgenin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D004195:Disease Models, Animal; D005911:Gliosis / Q000188:drug therapy / Q000473:pathology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D009410:Nerve Degeneration / Q000188:drug therapy / Q000473:pathology; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D058225:Plaque, Amyloid / Q000187:drug effects* / Q000473:pathology; D016548:Prosencephalon / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051381:Rats; D020318:Rats, Long-Evans; D013150:Spirostans; D016875:tau Proteins / Q000378:metabolism
C514145:(22R, 25R)-20alpha-spirost-5-en-3beta-yl hexanoate; D002208:Caproates; C489131:Mapt protein, rat; D018696:Neuroprotective Agents; D013150:Spirostans; D016875:tau Proteins; D004144:Diosgenin