Alzheimer's disease (AD) is a progressive disorder that affects the brain and leads to cognitive decline and memory loss, with postmenopausal women being unduly affected. Estrogen is believed to exert Show more
Alzheimer's disease (AD) is a progressive disorder that affects the brain and leads to cognitive decline and memory loss, with postmenopausal women being unduly affected. Estrogen is believed to exert neuroprotective effects by influencing amyloid-beta accumulation, tau hyperphosphorylation, oxidative stress, synaptic function, neuroinflammation, and brain-derived neurotrophic factor (BDNF) signalling. This review examines the role of estrogen in AD pathogenesis among postmenopausal women. A systematic literature search was conducted using PubMed, Scopus, and Web of Science. Keywords included "estrogen", "Alzheimer's disease", "neuroprotection", "amyloid-beta," and "BDNF." Inclusion criteria were peer-reviewed studies from the past 10 years focusing on estrogen's effects on AD mechanisms, neurobiology, and therapeutic relevance. Articles were screened by title and abstract. Followed by a full-text review to ensure methodological rigour and relevance. Evidence indicates that estrogen reduces amyloid beta burden, inhibits tau phosphorylation, mitigates oxidative stress, preserves synaptic connectivity, and suppresses neuroinflammation. Estrogen also modulates ApoE-linked lipid metabolism and enhances BDNF signalling, supporting neuronal survival and cognitive resilience. Declining estrogen after menopause increases vulnerability to AD. Understanding estrogen's neuroprotective mechanisms may support targeted therapeutic strategies. Hormone replacement therapy (HRT) and selective estrogen receptor modulators (SERMs) show potential, but further research is needed to optimise timing, dosage, and patient selection in postmenopausal AD prevention and management. Show less
The gene for receptor tyrosine kinase ErbB2 is amplified in breast and ovarian tumours. The linear pathway by which signals are transduced through ErbB2 are well known. However, second generation ques Show more
The gene for receptor tyrosine kinase ErbB2 is amplified in breast and ovarian tumours. The linear pathway by which signals are transduced through ErbB2 are well known. However, second generation questions that address spatial aspects of signaling remain. To address this, we have undertaken a mass spectrometry approach to identify phosphoproteins specific for ErbB2 using the inhibitors Lapatinib and CP724714 in ovarian cancer cells. The ErbB2 specific proteins identified in SKOV-3 cells were Myristoylated alanine-rich C-kinase substrate, Protein capicua homolog, Protein peptidyl isomerase G, Protein PRRC2C, Chromobox homolog1 and PRP4 homolog. We have evaluated three phosphoproteins PKM2, Aldose reductase and MARCKS in SKOV-3 cells. We observed that PKM2 was phosphorylated by EGF but was not inhibited by Lapatinib and CP724714. The activity of aldose reductase in reducing NADPH as a substrate was significantly higher in EGF stimulated cells which was inhibited by Lapatinib and CP724714 but not by Geftinib (EGFR inhibitor). MARCKS was phosphorylated on stimulation of SKOV-3 cells with EGF that was inhibited by Lapatinib and CP724714 which was dependent on the kinase activity of ErbB2. These results have identified phosphoproteins that are specific to ErbB2 which have not been previously reported and sets the basis for future experiments. Show less