Alzheimer’s disease (AD) and cancer are among the leading causes of human death around the world. While neurodegeneration is the main feature of AD, the most important characteristic of malignant tumors is cell proliferation, placing these two diseases in opposite sides of cell division spectrum. Interestingly, AD and cancer’s pathologies consist of a remarkable common feature and that is the presence of active cell cycle in both conditions. In an in vitro model of primary adult neuronal culture, we previously showed that treating cell with beta amyloid forced neurons to start a cell cycle. Instead of cell division, however, neuronal cell cycle was aborted and a massive neurodegeneration was left behind as the consequence. A high level of cell cycle entry, which is a requirement for cancer pathogenesis, was reported in clinically diagnosed cases of AD, leading to neurodegeneration. The diverse clinical manifestation of a similar etiology, have puzzled researchers for many years. In fact, the evidence showed an inverse association between AD and cancer prevalence, suggesting that switching pathogenesis toward AD protects patients against cancer and vice versa. In this mini review, we discussed the possibility of involvement of cell proliferation and survival dysregulation as the underlying mechanism of neurodegeneration in AD, and the leading event to develop both disorders’ pathology. As examples, the role of phosphoinositide 3 kinase/Akt/ mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathway in cell cycle re-entry and blocking autophagy are discussed as potential common intracellular components between AD and cancer pathogenesis, with diverse clinical diagnosis.

Hyperphosphorylation of tau is one of the main hallmarks for Alzheimer's disease (AD) and many other tauopathies. Norepinephrine (NE), a stress-related hormone and 17-β-estradiol (E2) thought to influence tau phosphorylation (p-tau) and AD pathology. The controversy around the impact of NE and E2 requires further clarification. Moreover, the combination effect of physiological and psychological stress and estrogen alteration during menopause, which affect p-tau, has not been addressed. Exposure to E2 is believed to reduce NE release, however, the link between these two hormones and AD at cellular level was also remained unknown. Here, we examined whether NE and E2 treatment of differentiated SH-SY5Y cells affected tau phosphorylation. The involvement of adenosine monophosphate kinase protein kinase (AMPK) and target of Rapamycin (mTOR) as the possible mechanisms, underlying this effect was also investigated. Subsequent to SH-SY5Y differentiation to mature neurons, we treated the cells with NE, E2 and NE plus E2 in presence and absence of Compound C and Rapamycin. Cell viability was not affected by our treatment while our Western blot and immunofluorescent findings showed that exposure to NE and E2 separately, and in combination enhanced p-tau (Ser) and (Ser)/tau but not (Ser/Thr)/tau. Blocking AMPK by Compound C reduced p-tau (Ser) and (Ser), while GSK-3β and PP2A activities were remained unchanged. We also found that blocking mTOR by Rapamycin did not change increased p-tau (Ser) and (Ser) due to NE + E2 treatment. Collectively, our results suggested that tau hyperphosphorylation due to exposure to NE/E2 was mediated by AMPK, the main energy regulator of cells during stress with no significant involvement of mTOR, GSK-3β and PP2A.

In healthcare settings, the importance of effective management cannot be overstated. It plays a pivotal role in guaranteeing the provision of top-notch care, maximizing resource utilization, and enhancing patient outcomes. This article aims to offer a comprehensive overview of management strategies employed in healthcare organizations, encompassing both clinical and non-clinical aspects. By delving into the roles and responsibilities of healthcare managers, examining clinical management techniques, and emphasizing the significance of non-clinical management practices, we shed light on the criticality of integrating both approaches with the aim of attaining optimal healthcare outcomes through a harmonious blend of clinical and non-clinical management methodologies.

Background: Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by the accumulation of hyperphosphorylated tau (p-tau) in neurofibrillary tangles and beta-amyloid plaques. The role of oxidative stress (OS) in AD progression remains unclear. Methods: Using SH-SY5Y human neuroblastoma cells as an in vitro model, we investigated the impact of OS on tau phosphorylation. Mature neurons were exposed to varying concentrations of hydrogen peroxide for different durations (1-5 days) to simulate OS. Western blot analysis was employed to quantify key signalling pathways (LKB1, AMPK, and Akt) and antioxidant enzymes (SOD2, p1, p4, and catalase). Results: Prolonged OS exposure resulted in tau hyperphosphorylation at Ser262, a tau residue sensitive to AMPK, despite initial dephosphorylation. Treatment with compound C (CC), an AMPK inhibitor, prevented this effect. OS activated LKB1 and AMPK, enhanced by CC and rapamycin, while CC and rapamycin suppressed OS-induced Akt activity. SOD2, the primary defence against OS, increased, whereas p1 and catalase, the secondary defence, decreased. P4 activity remained unchanged. Notably, CC consistently reduced antioxidant enzyme activity across experimental groups. Conclusion: OS activates the LKB1, AMPK, and Akt signalling pathways. The interplay between LKB1’s stimulatory effect and Akt’s inhibitory effect on AMPK leads to AMPK activation and subsequent tau hyperphosphorylation. AMPK facilitates the protective response mediated by SOD2 against OS, but prolonged OS exposure induces tau hyperphosphorylation. Therefore, OS likely serves as a trigger for AD pathology.