Amyloid precursor protein 17-mer peptide ameliorates hippocampal neurodegeneration in ovariectomized rats.
Amyloid precursor protein 17-mer peptide (APP 17-mer peptide) is an active fragment of amyloid precursor protein (APP) in the nervous system that mediates various neuronal activities and functions. Estrogen deprivation during menopause disproportionately increases the risk of many neurodegenerative diseases, including Alzheimer's disease (AD). Currently, therapeutic approaches to treat Alzheimer's disease are less than effective. We have previously shown that APP 17-mer peptide participates in neuronal function in aged-hippocampal neurons. In this study, we investigate the effects of estrogen and APP 17-mer peptide on hippocampal neurodegeneration in ovariectomized rats. The results showed that decreases in learning and memory function in ovariectomized rats were associated with degenerative changes in hippocampal neurons. Estrogen deprivation also enhances apoptotic cell death and decreases expression of the anti-apoptotic protein Bcl-2. Administration of APP 17-mer peptide ameliorates changes associated with estrogen deprivation without affecting estrogen levels. These results indicate that APP 17-mer peptide may prevent neurodegeneration caused by estrogen deficiency. Our findings also suggest that estrogen deficiency-induced neurodegeneration is regulated by activation of an intracellular "cross talk" signaling pathway, connecting neurotrophins with APP 17-mer peptide.
Meng
Yan
Y
Central Laboratory, Xuanwu Hospital of Capital Medical University, Key Laboratory for Neurodegenerative Disease of Ministry of Education, #45 Changchun Street, Xuanwu District, Beijing 100053, China.
Wang
Rong
R
Yang
Fang
F
Ji
Zhi-Juan
ZJ
Fang
Li
L
Sheng
Shu-Li
SL
D016564:Amyloid beta-Protein Precursor / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D017209:Apoptosis; D015415:Biomarkers / Q000378:metabolism; D004958:Estradiol / Q000097:blood / Q000172:deficiency; D004967:Estrogens / Q000097:blood / Q000172:deficiency; D005260:Female; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018782:Maze Learning / Q000187:drug effects; D009410:Nerve Degeneration / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D009414:Nerve Growth Factors / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010052:Ovariectomy; D010446:Peptide Fragments / Q000494:pharmacology* / Q000627:therapeutic use; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D016564:Amyloid beta-Protein Precursor; D015415:Biomarkers; D004967:Estrogens; D009414:Nerve Growth Factors; D010446:Peptide Fragments; D019253:Proto-Oncogene Proteins c-bcl-2; C446879:amyloid beta-protein precursor 695 (319-339); D004958:Estradiol