Conferencia - Biología de sistemas de los trastornos neurodegenerativos
Secretaría de Ciencia・7 minutes read
The National Council of Humanities, Sciences, and Technologies is showcasing Mexican scientific advancements through conferences, emphasizing the importance of research in understanding neurodegenerative diseases like Alzheimer’s, particularly focusing on the role of myelination and lipid metabolism. Dr. José Dávila Valderrain presented his findings, highlighting the intricate relationship between genetic factors, such as the APOE gene variant, and the mechanisms influencing Alzheimer’s disease, while stressing the need for preventive measures and further research in this area.
Insights
- The National Council of Humanities, Sciences, and Technologies has initiated a series of conferences to highlight Mexican scientific progress, encouraging participation from both emerging and seasoned researchers, as stated by Dr. María Elena Álvarez, who underscored the importance of fostering scientific development in Mexico.
- Dr. José Dávila Valderrain, a prominent researcher in neurodegenerative disorders, particularly Alzheimer’s disease, shared insights on the complexity of these diseases, noting that Alzheimer’s can develop silently over decades before symptoms arise, which complicates both comprehension and treatment.
- Dávila's research employs advanced techniques like single-cell sequencing and cellular reprogramming to investigate the role of cholesterol metabolism and myelination in Alzheimer’s, revealing significant connections between genetic mutations, cholesterol accumulation, and the functionality of brain cells, specifically oligodendrocytes.
- The findings suggest that maintaining cognitive engagement and a healthy lifestyle can mitigate the risk of neurodegenerative diseases, while the study also calls for a broader exploration of various hypotheses, including the myelogenic and cholinergic theories, to deepen understanding of Alzheimer’s pathology beyond the established amyloid hypothesis.
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Recent questions
What is Alzheimer’s disease?
Alzheimer’s disease is a progressive neurodegenerative disorder that primarily affects memory and cognitive function. It is characterized by the accumulation of beta-amyloid plaques and tau protein tangles in the brain, leading to the death of neurons and a decline in mental abilities. Symptoms often develop slowly and can include memory loss, confusion, and changes in behavior. The disease typically manifests in older adults, with risk factors including age, genetics, and lifestyle choices. Understanding Alzheimer’s is crucial as it is a leading cause of dementia, and ongoing research aims to uncover its underlying mechanisms and potential treatments.
How can I prevent Alzheimer’s disease?
Preventing Alzheimer’s disease involves adopting a healthy lifestyle that promotes brain health. Key strategies include maintaining regular cognitive activity, engaging in social interactions, and participating in physical exercise. A balanced diet rich in fruits, vegetables, whole grains, and healthy fats can also support cognitive function. Additionally, managing cardiovascular health by controlling blood pressure, cholesterol levels, and diabetes is important. While there are currently no definitive cures for Alzheimer’s, these preventive measures can help reduce the risk and delay the onset of symptoms, emphasizing the importance of proactive health management as one ages.
What are the symptoms of Alzheimer’s?
Symptoms of Alzheimer’s disease typically begin with mild memory loss and confusion, gradually progressing to more severe cognitive decline. Individuals may experience difficulty in remembering recent events, trouble with language, and challenges in performing familiar tasks. As the disease advances, symptoms can include disorientation, mood swings, changes in personality, and difficulty recognizing loved ones. In the later stages, individuals may lose the ability to communicate and require assistance with daily activities. Recognizing these symptoms early is crucial for diagnosis and intervention, as timely support can improve quality of life for those affected.
What causes Alzheimer’s disease?
Alzheimer’s disease is caused by a combination of genetic, environmental, and lifestyle factors that lead to brain changes over time. The hallmark features of the disease include the accumulation of beta-amyloid plaques and tau tangles, which disrupt communication between neurons and trigger inflammation. Genetic mutations, particularly in the APOE gene, can increase the risk of developing Alzheimer’s. Other contributing factors include age, with the risk increasing significantly after 65, and lifestyle choices such as diet, exercise, and cognitive engagement. Understanding these causes is essential for developing effective prevention and treatment strategies.
What is myelination and its role in Alzheimer’s?
Myelination is the process by which neurons are coated with a fatty layer called myelin, which is essential for efficient signal transmission in the nervous system. In the context of Alzheimer’s disease, alterations in myelination can impact neuronal function and contribute to cognitive decline. Research has shown that myelination processes evolve over time and can be influenced by genetic factors, such as mutations in the APOE gene. Disruptions in myelination may lead to increased vulnerability of neurons to damage, highlighting the importance of understanding myelination in the study of Alzheimer’s and other neurodegenerative diseases.
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Summary
00:00
Mexican Conferences Highlight Advances in Neuroscience
- The national council of humanities, sciences, and technologies recently approved a series of conferences to showcase Mexican scientific advancements, inviting both young and experienced researchers to participate.
- Attendees are encouraged to register via a link on Facebook and YouTube to receive a certificate, requiring their email, first surname, and first name for processing.
- Dr. María Elena Álvarez welcomed participants, emphasizing the importance of scientific and humanistic development in Mexico and the council's commitment to supporting young researchers.
- Dr. José Dávila Valderrain, the first speaker, holds a biology degree from Universidad Autónoma de Nuevo León and a doctorate in biomedical sciences from Universidad Nacional Autónoma de México, completed in 2015.
- Dávila was a postdoctoral researcher at MIT's Artificial Intelligence and Computational Science Laboratory and currently leads a research group at the Neurogenomics Research Center in Milan, Italy.
- His research focuses on neurodegenerative disorders, particularly Alzheimer’s disease, exploring the evolution and development of the human brain to understand its dysfunction.
- Dávila highlighted the distinction between neuropsychiatric disorders, like schizophrenia and depression, and neurodegenerative diseases, which typically manifest later in life, often decades after initial development.
- Alzheimer’s disease, a common cause of dementia, can develop over 20 to 30 years before clinical symptoms appear, complicating its understanding and treatment.
- The research employs single-cell sequencing technologies to analyze postmortem brain samples, allowing for detailed examination of gene expression at the individual cell level.
- Dávila's approach integrates various biological scales, combining genomic data, artificial intelligence, and animal models to better understand the complex interactions within the brain related to neurodegenerative diseases.
28:52
Myelination and Alzheimer’s Disease Insights Revealed
- Molecular alterations in Alzheimer’s disease can be analyzed through transcriptional profiles and computational clustering to identify different cell types and their gene expression levels.
- The study highlights the significance of myelination, a process involving the coating of neurons with a lipid layer, which is crucial for neuronal function and signal transmission.
- Myelination is linked to developmental milestones, such as increased brain myelination in pianists and children learning to speak or walk, indicating its role in skill acquisition.
- Genetic mutations associated with Alzheimer’s disease, particularly in the APOE gene, show polymorphism in the population, with variant 4 increasing Alzheimer’s risk by 3 to 12 times.
- The study found that cholesterol metabolism is altered in individuals with the APOE variant 4, with gene expression changes being dose-dependent based on the number of gene copies.
- Lipidomics analysis confirmed increased levels of specific lipids associated with cholesterol in individuals carrying the APOE variant, indicating potential physiological relevance.
- Transgenic mice were used to study the effects of the APOE variant, confirming abnormal cholesterol accumulation in oligodendrocytes, which are crucial for myelination.
- The research utilized cellular reprogramming to create induced pluripotent stem cells (iPSCs) with the APOE mutation, allowing for controlled experiments on oligodendrocyte function.
- In vitro experiments demonstrated that combining neurons and oligodendrocytes can recreate myelination processes, providing insights into how mutations affect brain cell interactions.
- The study emphasizes the need for further research to understand the biological mechanisms behind myelination alterations in Alzheimer’s and their implications for other neurodegenerative diseases.
54:02
Cholesterol's Role in Myelination and Alzheimer's
- Organoids and organ-on-a-chip systems are related, both involving cell cultures that combine multiple cell types in three-dimensional structures for research purposes.
- Using simpler systems instead of organoids can enhance reproducibility and focus on specific cell types, such as oligodendrocytes and neurons, for studying myelination.
- Mutations can be induced selectively in specific cell types to isolate their effects, allowing researchers to observe myelination deficiencies linked to oligodendrocyte mutations.
- Cholesterol accumulation and myelination defects were identified, with research suggesting that either excessive production or improper transport of cholesterol could be responsible for these issues.
- A collection of chemicals was used to differentiate between cholesterol biosynthesis and transport, revealing that facilitating transport corrected cholesterol accumulation and myelination defects.
- Cyclodextrin, a small chemical, was tested in vitro and in transgenic mice, showing improvements in cholesterol accumulation, myelination, and cognitive functions like learning and memory.
- The study proposed a model where cholesterol accumulation in oligodendrocytes leads to intracellular stress, affecting myelination and linking it to Alzheimer’s disease risk factors.
- Myelination processes evolve over 40 years, peaking around age 45, after which it declines, making neurons more vulnerable to alterations associated with Alzheimer’s.
- Environmental enrichment, such as providing cognitive stimulation and social interaction for mice, may enhance myelination and cognitive reserve, potentially reducing Alzheimer’s risk.
- Ongoing research is exploring the impact of endocrine factors, like estrogens, on myelination decline and their relevance to Alzheimer’s pathology, though technical challenges exist in studying these effects.
01:17:13
Challenges and Insights in Alzheimer’s Research
- The discussion revolves around the challenges of studying cancer treatment side effects and the potential for using volumetry and intensity as markers for understanding these effects in living subjects.
- Concerns are raised about the reliability of RNA levels found in nuclei, as they may be low due to export to the cytoplasm, affecting the accuracy of experimental results.
- The gene for the E protein is linked to Alzheimer’s disease, particularly regarding the accumulation of beta-amyloid plaques, which are central to one of the disease's hypotheses.
- The study analyzed the relationship between tau protein truncation and Alzheimer’s, noting that intracellular fiber formation in neurons correlates more with cognitive issues than extracellular amyloid plaques.
- The research emphasizes the importance of computational methodologies to analyze complex data, especially when distinguishing between technical and biological zeros in gene expression.
- The amyloid hypothesis is acknowledged as relevant, particularly for early-onset Alzheimer’s, but the study suggests that other processes may also contribute significantly to the disease.
- The research design included a balanced selection of male and female subjects to assess the effects of genotype and pathology on lipid metabolism and Alzheimer’s progression.
- The study highlights the role of lipid metabolism in brain function, noting that alterations in lipid processing can have significant consequences for cellular health and Alzheimer’s pathology.
- The discussion critiques the focus on cholesterol-related theories over other hypotheses, such as the myelogenic theory and cholinergic theory, which also warrant investigation in Alzheimer’s research.
- Preventive measures for Alzheimer’s include maintaining cognitive activity, regular exercise, and a healthy diet, as there are currently no effective cures or treatments for the disease.
01:40:17
Aging Cholesterol Proteins and Alzheimer's Risk
- Maintaining a healthy lifestyle and cognitive activity during aging can protect against neurodegenerative diseases like Alzheimer's, emphasizing the importance of social engagement.
- Statins are widely used to lower cholesterol levels, raising questions about their potential impact on reducing Alzheimer's incidence, though no definitive studies confirm this correlation.
- There are sex differences in cholesterol processing, with men showing a greater propensity for certain cholesterol types, while women are more prone to Alzheimer's, warranting further epidemiological investigation.
- Cholesterol transport mechanisms differ between the brain and the body, with various apolipoproteins involved, complicating the relationship between cholesterol levels and neurodegeneration.
- A single amino acid change in a protein can significantly affect Alzheimer's risk, with the E2 variant being protective, though it may increase susceptibility to other diseases.
- Computer simulations are used to study protein behavior at the atomic level, examining how mutations affect protein structure and dynamics over time.
- The degree of protein compaction is crucial for lipid binding, with risk genotypes showing increased compaction compared to reference genotypes, affecting their functionality.
- Evolutionary genetics suggests that older genetic variants are typically more common, with the E4 variant linked to Alzheimer's risk being prevalent in humans but not in other species.
- Research is ongoing to understand how ancestral protein variants from species like chimpanzees differ from human variants, particularly regarding their structural properties and disease implications.
- The study aims to connect evolutionary changes in protein function with pathogenic consequences in humans, exploring molecular circuitry differences across species to better understand Alzheimer's risk.
02:03:57
Exploring Protein Interactions in Cellular Signaling
- The research focuses on understanding protein interactions with lipids and receptors, emphasizing how these interactions affect cellular signaling across different species and cell types.
- A computational approach is employed to analyze complex data, with a specific emphasis on recruiting individuals with both biological and mathematical expertise to enhance research capabilities.
- The research group in Milan encourages collaboration and invites interested doctoral students to join, while also promoting access to various scientific journals for broader engagement in the scientific community.
