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Dementia

The Fine Control of Cell Mechanics Unveiled

Our skin and mucous membranes are protected by epithelial cells. This ‘barrier’ tissue performs its function thanks to specialized structures called ‘junctions’. They ensure cell cohesion and regulate exchanges across the space between cells. Researchers have studied the role of a specific protein, gamma-actin, in the organization and mechanics of epithelial cells and their junctions. Their work reveals a mechanism of interdependence of different forms of the cytoskeletal proteins actin and myosin, and their functions. The team also demonstrates the key role of gamma-actin in the rigidity of cell membranes and the dynamics of junctional proteins, which may provide a mechanism of hearing loss.

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The human body is protected by an intricate network of tissues, one of which is the epithelium – a layer of tightly bound cells that covers our skin and mucous membranes. The key to this “barrier” tissue’s effectiveness lies in its specialized structures called junctions, which ensure cell cohesion and regulate exchanges between cells. Researchers at the University of Geneva (UNIGE), collaborating with institutions in Singapore and Germany, have delved into the role of a specific protein – gamma-actin – in organizing and maintaining the mechanics of epithelial cells and their junctions.

The study, published in Nature Communications, reveals an intricate mechanism where different forms of cytoskeletal proteins actin and myosin are interdependent, influencing each other’s functions. Moreover, the researchers demonstrate that gamma-actin plays a crucial role in regulating cell membrane rigidity and junctional protein dynamics – findings that could potentially shed light on mechanisms behind hearing loss.

The epithelium is a vital tissue that lines our skin and organs, providing essential protection against external threats such as pathogens. Its tightness relies heavily on the presence of “adherens” and “tight junctions,” which are protein-based locks that link neighboring cells together. These junctions regulate molecular traffic in and out of organs – for example, facilitating nutrient absorption in the intestine or filtering substances in the kidneys.

Researchers from the UNIGE laboratory led by Associate Professor Sandra Citi aimed to understand how tight junctions interact with the cytoskeleton – the internal framework of cells – to regulate cell architecture and various epithelial functions. The team’s study focused on gamma-actin, one of the components of the cytoskeleton, and discovered that its absence triggers increased production of beta-actin and a specific form of myosin.

“Changes made the apical membrane less stiff and certain constituents of the tight junctions more mobile, without affecting the barrier formed by these junctions,” explains Marine Maupérin, postdoctoral fellow at UNIGE and first author of the study. The researchers found that gamma-actin confers increased rigidity to the apical membrane by forming a network of filaments stronger and stiffer than those made up of beta-actin filaments.

This result is particularly interesting because the stiffness of the apical membrane is essential for auditory function, says Sandra Citi. Indeed, mice deficient in gamma-actin display altered architecture of the apical surface of epithelial cells and progressive hearing loss. A stiffer cortical membrane may be required to withstand constant mechanical stimuli to which hair cells lining the inner ear are exposed.

A deeper investigation into the role of gamma-actin in maintaining cell integrity could thus help understand pathologies of hearing loss, for example.

Alzheimer's

The Surprising Link Between Curiosity and Healthy Aging

Psychology literature has shown that curiosity tends to decline with age. Psychologists shows one type of curiosity can increase well into old age, contradicting prior research. Older adults who maintain curiosity and want to learn new things relevant to their interests may be able to offset or even prevent Alzheimer’s disease. Conversely, those who show muted curiosity and disinterest may be at risk for dementia.

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The secret to aging successfully may not be what you think. Instead of focusing on physical exercise or mental stimulation alone, research suggests that cultivating curiosity can play a significant role in maintaining cognitive health and even preventing Alzheimer’s disease. An international team of psychologists has found that older adults who maintain a curious mindset and seek out new knowledge relevant to their interests may be able to offset or prevent dementia.

This finding challenges prior research that suggested curiosity decreases with age. The study, published in the journal PLOS One, was led by UCLA psychologist Alan Castel and involved a large sample of participants between the ages of 20 and 84. The researchers aimed to tease apart two types of curiosity: trait curiosity (a general level of inquisitiveness) and state curiosity (a momentary feeling of curiosity experienced when engaging with specific topics).

To assess these forms of curiosity, the researchers asked participants to complete an online questionnaire and guess answers to hard trivia questions. Analysis showed that while trait curiosity did decline across the adult lifespan, state curiosity increased sharply after middle age and continued upward well into old age.

The study’s lead author, Mary Whatley, notes that this finding may be related to selectivity theory, which suggests that as people get older, they become more selective about what they want to learn. This aligns with research on lifelong learning, where many older adults engage in activities like taking classes or picking up hobbies.

Castel’s own work on memory has shown that people tend to quickly forget information that doesn’t engage their curiosity. Anecdotally, many older adults report that staying curious is crucial for maintaining cognitive health and preventing dementia.

This study was supported by the National Institutes of Health’s National Institute on Aging, the Leverhulme Trust, and the Alexander von Humboldt Foundation. The findings suggest that cultivating curiosity can be a key factor in healthy aging and may even help prevent or offset Alzheimer’s disease.

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Brain Injury

Uncovering the Aggressive Nature of Glioblastoma: ZIP4’s Role in Brain Tumor Growth

Researchers detail their discoveries about why the brain tumor glioblastoma is so aggressive. Their findings center on ZIP4, a protein that transports zinc throughout the body and sets off a cascade of events that drive tumor growth.

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In a groundbreaking study published in the Proceedings of the National Academy of Sciences (PNAS), University of Oklahoma researchers have made a significant discovery about what makes glioblastoma, the deadliest form of brain cancer, so aggressive. The findings center on ZIP4, a protein that transports zinc throughout the body and sets off a chain reaction that drives tumor growth.

Glioblastomas account for about half of all malignant brain tumors, with a median survival rate of 14 months. Surgery is often challenging, and patients almost always experience a relapse. By better understanding why these brain tumors are so aggressive, researchers hope to open up paths for new treatments.

In normal conditions, ZIP4 plays a positive role, transporting and maintaining the right amount of zinc for good health. However, when brain cancer is present, ZIP4 takes on a different role. In the case of glioblastoma, it triggers a series of events that contribute to the tumor’s aggressive growth.

“Everything starts with the fact that ZIP4 is overexpressed in glioblastoma,” says senior author Min Li, Ph.D., a professor of medicine, surgery, and cell biology at the University of Oklahoma College of Medicine. “That triggers all these downstream events that help the tumor to grow.”

Li’s research team tested a small-molecule inhibitor that targets ZIP4 and TREM1, a protein involved in immune responses. The inhibitor attached to both proteins, stopping their actions and slowing tumor growth. This suggests that ZIP4 and TREM1 may be promising therapeutic targets.

Neurosurgeon Ian Dunn, M.D., executive dean of the OU College of Medicine and co-author of the study, says the findings are an encouraging step toward combating this debilitating cancer. “These results are really exciting in such a debilitating cancer. The hope and promise is to translate these findings to novel treatment approaches to improve the lives of our patients.”

This discovery is significant not only for glioblastoma but also for pancreatic cancer research, as ZIP4 has been a focus of Li’s work on this disease for many years. He found that overexpression of ZIP4 causes pancreatic cancer cells to be more resistant to chemotherapy and prompts tumor cells to transform themselves so they can stealthily travel to the body’s other organs.

The researchers hope that their findings will lead to new treatment approaches for glioblastoma and potentially other types of cancer, improving the lives of patients affected by these devastating diseases.

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Alzheimer's

“Unlocking Brain Resilience: Researchers Discover CLU Protein’s Potential to Protect Against Alzheimer’s Disease”

Recently approved Alzheimer’s drugs offer a step forward for treating the disease, but new therapeutic strategies are needed to complement them and provide personalized therapeutic approaches. Researchers have identified a potential strategy to protect against Alzheimer’s disease by increasing the clusterin protein (CLU).

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As scientists continue to search for effective treatments for Alzheimer’s disease, a recent study has shed light on a promising new approach. Researchers at Mass General Brigham have discovered that increasing levels of the “CLU” (clusterin) protein may protect against cognitive decline and potentially provide a complementary therapy to existing treatments.

Led by Dr. Tracy Young-Pearse, the research team used various models, including human brain tissue from over 700 participants and animal models, to uncover the molecular role of CLU in protecting against neurodegeneration. Their findings suggest that increasing CLU can prevent inflammatory interactions between brain cells called astrocytes and microglia, which are associated with heightened inflammation.

The study’s results have significant implications for the design and testing of new therapeutic strategies for Alzheimer’s disease. As Dr. Young-Pearse noted, “Increasing clusterin has the potential to prevent cognitive decline in a way that is different than and complementary to anti-amyloid therapies to promote brain resilience.”

CLU may also be beneficial for treating other age-related brain diseases, many of which share similar mechanisms of neuroinflammatory dysregulation. The researchers emphasize the importance of personalized therapeutic approaches, as individuals’ responses to CLU upregulation vary based on their genetics.

The study’s findings provide a crucial step forward in the search for effective treatments for Alzheimer’s disease and other age-related brain diseases. By understanding the role of CLU in protecting against neurodegeneration, researchers can develop new strategies to promote brain resilience and potentially prevent cognitive decline.

In conclusion, the discovery of CLU’s potential therapeutic benefits offers new hope for individuals affected by Alzheimer’s disease and other age-related brain disorders. Further research is necessary to fully explore this promising approach, but the findings of this study mark an important milestone in the pursuit of effective treatments for these debilitating diseases.

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