Apolipoprotein E may be a critical factor in hormone therapy neuroprotection.
In this review we examine the evidence for ovarian hormone neuroprotection in chronic neurological diseases, including stroke. We propose that neuroprotection may involve the ability of estrogens to modulate apolipoprotein E (apoE) and its receptor, the low density lipoprotein receptor related protein (LRP). Results from numerous studies have demonstrated that (1) nerve regeneration is severely delayed in apoE-gene knockout (KO) mice as compared to wild-type (WT) littermates; (2) 17beta estradiol replacement in ovariectomized mice resulted in a significant increase in levels of apoE and LRP, in the olfactory bulb (OB) and other brain areas; (3) estradiol treatment increased both apoE and neurite outgrowth in cortical and olfactory neuronal cultures; and (4) estradiol treatment had no effect on neurite outgrowth in cultures deprived of apoE or in the presence of apoE4. In essence these studies suggest that apoE is a critical intermediary for the beneficial effects of 17beta estradiol on nerve repair, which can lead to functional reorganization (plasticity). Future studies of HT should evaluate the effects of apoE genotype and production estradiol on neuroprotection.
Center for Alzheimer's Disease and Related Disorders, Department of Neurology, Southern Illinois University School of Medicine, P.O. Box 19643, Springfield, IL 62794-9643, USA. rstruble@siumed.edu
Robert G
RG
Struble
Craig
C
Cady
Britto P
BP
Nathan
Mary
M
McAsey
D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D002908:Chronic Disease; D003704:Dementia / Q000188:drug therapy / Q000503:physiopathology / Q000517:prevention & control; D015914:Estrogen Replacement Therapy; D005260:Female; D006728:Hormones / Q000627:therapeutic use*; D006801:Humans; D008593:Menopause / Q000502:physiology; D008597:Menstrual Cycle / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D023421:Models, Animal; D009422:Nervous System Diseases / Q000503:physiopathology; D018696:Neuroprotective Agents; D020521:Stroke / Q000503:physiopathology
D001057:Apolipoproteins E; D006728:Hormones; D018696:Neuroprotective Agents