Cellular and molecular basis of estrogen's neuroprotection. Potential relevance for Alzheimer's disease.
Alzheimer's disease (AD) is one of the most common types of dementia among the aged population, with a higher prevalence in women. The reason for this latter observation remained unsolved for years, but recent studies have provided evidence that a lack of circulating estrogen in postmenopausal women could be a relevant factor. Moreover, follow-up studies among postmenopausal women who had received estrogen-replacement therapy (ERT), suggested that they had a markedly reduced risk of developing AD. In addition, studies among older women who already had AD indeed confirmed that a decrease in estrogen levels was likely to be an important factor in triggering the pathogenesis of the disease. In this review article, we will discuss the evidence suggesting that estrogen may have a protective role against AD, mainly through its action as: a trophic factor for cholinergic neurons, a modulator for the expression of apolipoprotein E (ApoE) in the brain, an antioxidant compound decreasing the neuronal damage caused by oxidative stress, and a promoter of the physiological nonamyloidogenic processing of the amyloid precursor protein (APP), decreasing the production of the amyloid-beta-peptide (A beta), a key factor in the pathogenesis of AD.
Inestrosa
N C
NC
Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile.
Marzolo
M P
MP
Bonnefont
A B
AB
D000368:Aged; D000544:Alzheimer Disease / Q000453:epidemiology / Q000503:physiopathology* / Q000517:prevention & control*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000975:Antioxidants; D001057:Apolipoproteins E / Q000235:genetics; D015914:Estrogen Replacement Therapy; D004967:Estrogens / Q000502:physiology* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D008297:Male; D009474:Neurons / Q000502:physiology; D018696:Neuroprotective Agents; D017698:Postmenopause; D015995:Prevalence; D012727:Sex Characteristics
D016564:Amyloid beta-Protein Precursor; D000975:Antioxidants; D001057:Apolipoproteins E; D004967:Estrogens; D018696:Neuroprotective Agents