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Neural Regeneration Research Jun 2024Mature oligodendrocytes form myelin sheaths that are crucial for the Insulation of axons and efficient signal transmission in the central nervous system. Recent evidence...
Mature oligodendrocytes form myelin sheaths that are crucial for the Insulation of axons and efficient signal transmission in the central nervous system. Recent evidence has challenged the classical view of the functionally static mature oligodendrocyte and revealed a gamut of dynamic functions such as the ability to modulate neuronal circuitry and provide metabolic support to axons. Despite the recognition of potential heterogeneity in mature oligodendrocyte function, a comprehensive summary of mature oligodendrocyte diversity is lacking. We delve into early 20th-century studies by Robertson and Río-Hortega that laid the foundation for the modern identification of regional and morphological heterogeneity in mature oligodendrocytes. Indeed, recent morphologic and functional studies call into question the long-assumed homogeneity of mature oligodendrocyte function through the identification of distinct subtypes with varying myelination preferences. Furthermore, modern molecular investigations, employing techniques such as single cell/nucleus RNA sequencing, consistently unveil at least six mature oligodendrocyte subpopulations in the human central nervous system that are highly transcriptomically diverse and vary with central nervous system region. Age and disease related mature oligodendrocyte variation denotes the impact of pathological conditions such as multiple sclerosis, Alzheimer's disease, and psychiatric disorders. Nevertheless, caution is warranted when subclassifying mature oligodendrocytes because of the simplification needed to make conclusions about cell identity from temporally confined investigations. Future studies leveraging advanced techniques like spatial transcriptomics and single-cell proteomics promise a more nuanced understanding of mature oligodendrocyte heterogeneity. Such research avenues that precisely evaluate mature oligodendrocyte heterogeneity with care to understand the mitigating influence of species, sex, central nervous system region, age, and disease, hold promise for the development of therapeutic interventions targeting varied central nervous system pathology.
PubMed: 38934385
DOI: 10.4103/NRR.NRR-D-24-00055 -
Frontiers in Aging Neuroscience 2024Dementia is a progressive neurodegenerative condition, while metabolic syndrome (MetS) is characterized by a combination of metabolic abnormalities such as hypertension,...
BACKGROUND
Dementia is a progressive neurodegenerative condition, while metabolic syndrome (MetS) is characterized by a combination of metabolic abnormalities such as hypertension, high blood sugar, and obesity. There exists a connection and overlap between the two conditions in certain aspects, and both are influenced to varying degrees by the process of aging. This study presents an overview of the current research landscape regarding dementia and MetS through bibliometric analysis.
METHODS
A systematic search was conducted to retrieve relevant literature on dementia and MetS published between 1 January 2000, and 30 November 2023, from the Web of Science Core Collection database. Various bibliometric tools, including VOSviewer, CiteSpace, and the R software package "bibliometrix," were utilized for analysis.
RESULTS
A total of 717 articles were identified, showing an upward trend in annual publications. Leading contributors included the United States, Italy, and China, with institutions such as the University of California System at the forefront. The emerged as the top publisher, while research published in garnered significant citations. Noteworthy authors encompassed Panza, Francesco; Frisardi, Vincenza; and Feldman, Eva L, with Kristine Yaffe being the most cited author (280 citations). Recent studies have focused on themes like "gut microbiota," "neuroinflammation," "fatty acids," and "microglia."
CONCLUSION
This bibliometric analysis summarizes the foundational knowledge structure in the realm of dementia and MetS from 2000 to 2023. By highlighting current research frontiers and trending topics, this analysis serves as a valuable reference for researchers in the field.
PubMed: 38934020
DOI: 10.3389/fnagi.2024.1400589 -
Frontiers in Aging Neuroscience 2024Changes in everyday functioning constitute a clinically meaningful outcome, even in the early stages of Alzheimer's disease. Performance-based assessments of everyday...
Amyloid and tau burden relate to longitudinal changes in the performance of complex everyday activities among cognitively unimpaired older adults: results from the performance-based Harvard Automated Phone Task.
BACKGROUND
Changes in everyday functioning constitute a clinically meaningful outcome, even in the early stages of Alzheimer's disease. Performance-based assessments of everyday functioning might help uncover these early changes. We aimed to investigate how changes over time in everyday functioning relate to tau and amyloid in cognitively unimpaired older adults.
METHODS
Seventy-six cognitively unimpaired participants (72 ± 6 years old, 61% female) completed multiple Harvard Automated Phone Task (APT) assessments over 2.0 ± 0.9 years. The Harvard APT consists of three tasks, performed through an automated phone system, in which participants refill a prescription (APT-Script), select a new primary care physician (APT-PCP), and transfer money to pay a bill (APT-Bank). Participants underwent Pittsburgh compound-B and flortaucipir positron emission tomography scans at baseline. We computed distribution volume ratios for a cortical amyloid aggregate and standardized uptake volume ratios for medial temporal and neocortical tau regions. In separate linear mixed models, baseline amyloid by time and tau by time interactions were used to predict longitudinal changes in performance on the Harvard APT tasks. Three-way amyloid by tau by time interactions were also investigated. Lastly, we examined associations between tau and change in Harvard APT scores in exploratory voxel-wise whole-brain analyses. All models were adjusted for age, sex, and education.
RESULTS
Amyloid [unstandardized partial regression coefficient estimate (β) = -0.007, 95% confidence interval (95% CI) = (-0.013, -0.001)], and medial temporal tau [β = -0.013, 95% CI = (-0.022, -0.004)] were associated with change over time in years on APT-PCP only, i.e., higher baseline amyloid and higher baseline tau were associated with steeper rate of decline of APT-PCP. Voxel-wise analyses showed widespread associations between tau and change in APT-PCP scores over time.
CONCLUSION
Even among cognitively unimpaired older adults, changes over time in the performance of cognitively complex everyday activities relate to cortical amyloid and widespread cerebral tau burden at baseline. These findings support the link between Alzheimer's disease pathology and function and highlight the importance of measuring everyday functioning in preclinical disease stages.
PubMed: 38934017
DOI: 10.3389/fnagi.2024.1420290 -
Food Chemistry: X Oct 2024Most phenolic compounds in beans exist in complex, insoluble binding forms that bind to cell wall components ether, ester, or glucoside bonds. In the process of...
Most phenolic compounds in beans exist in complex, insoluble binding forms that bind to cell wall components ether, ester, or glucoside bonds. In the process of solid-state fermentation, can produce many hydrolase enzymes, such as α-amylase, pectinase, cellulase and β-glucosidase, which can effectively hydrolyze ether, ester or glucoside bond, release bound polyphenols, and increase polyphenol content in soybeans. When the fermentation conditions of soybean were fermentation time 12 days, inoculation amount 15% and initial pH 2, the content of free polyphenols in fermented soybean was 2.79 mg GAE/g d.w, which was 4.98 times that of unfermented soybean. The contents of bound polyphenols and total phenols in fermented soybean were 0.62 mg GAE/g d.w and 3.41 mg GAE/g d.w, respectively, which were 2.38 times and 4.16 times of those in unfermented soybean. At the same time, the inhibitory effect of free polyphenols in fermented soybean on acetylcholinesterase reached 91.51%. Thus, our results demonstrated that solid state fermentation and can be used as an effective way to increase soybean polyphenol content and combat Alzheimer's disease.
PubMed: 38933989
DOI: 10.1016/j.fochx.2024.101526 -
Frontiers in Neuroscience 2024Parkinson's disease (PD) is a common neurodegenerative disease with a rapid increase in incidence in recent years. Existing treatments cannot slow or stop the...
BACKGROUND
Parkinson's disease (PD) is a common neurodegenerative disease with a rapid increase in incidence in recent years. Existing treatments cannot slow or stop the progression of PD. It was proposed that neuroinflammation leads to neuronal death, making targeting neuroinflammation a promising therapeutic strategy. Our previous studies have demonstrated that rhein protects neurons by inhibiting neuroinflammation, and it has been found to exhibit neuroprotective effects in Alzheimer's disease and epilepsy, but its neuroprotective mechanisms and effects on PD are still unclear.
METHODS
PD animal model was induced by 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine (MPTP). ELISA, RT-qPCR, western blot and Immunofluorescence were used to detect the levels of inflammatory cytokines and M1 polarization markers. The protein expression levels of signaling pathways were measured by western blot. Hematoxylin-eosin (HE) staining showed that rhein did not damage the liver and kidney. Two behavioral tests, pole test and rotarod test, were used to evaluate the improvement effect of rhein on movement disorders. The number of neurons in the substantia nigra was evaluated by Nissl staining. Immunohistochemistry and western blot were used to detect tyrosine hydroxylase (TH) and α-synuclein.
RESULTS
Rhein inhibited the activation of MAPK/IκB signaling pathway and reduced the levels of pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α) and M1 polarization markers of microglia . In a mouse model of PD, rhein ameliorated movement disorders, reduced dopaminergic neuron damage and α-synuclein deposition.
CONCLUSION
Rhein inhibits neuroinflammation through MAPK/IκB signaling pathway, thereby reducing neurodegeneration, α-synuclein deposition, and improving movement disorders in Parkinson's disease.
PubMed: 38933815
DOI: 10.3389/fnins.2024.1396345 -
Frontiers in Immunology 2024Air pollution is an urgent concern linked to numerous health problems in low- and middle-income countries, where 92% of air pollution-related deaths occur. Particulate... (Review)
Review
Air pollution is an urgent concern linked to numerous health problems in low- and middle-income countries, where 92% of air pollution-related deaths occur. Particulate matter 2.5 (PM) is the most harmful component of air pollutants, increasing inflammation and changing gut microbiota, favoring obesity, type 2 diabetes, and Alzheimer's Disease (AD). PM contains lipopolysaccharides (LPS), which can activate the Toll-like receptor 4 (TLR4) signaling pathway. This pathway can lead to the release of pro-inflammatory markers, including interleukins, and suppressor of cytokine signaling-3 (SOCS3), which inhibits leptin action, a hormone that keeps the energy homeostasis. Leptin plays a role in preventing amyloid plaque deposition and hyperphosphorylation of tau-protein (p-tau), mechanisms involved in the neurodegeneration in AD. Approximately 50 million people worldwide are affected by dementia, with a significant proportion living in low-and middle-income countries. This number is expected to triple by 2050. This mini-review focuses on the potential impact of PM exposure on the TLR4 signaling pathway, its contribution to leptin resistance, and dysbiosis that exacerbates the link between obesity and AD.
Topics: Humans; Alzheimer Disease; Obesity; Leptin; Air Pollution; Particulate Matter; Toll-Like Receptor 4; Inflammation; Animals; Signal Transduction; Air Pollutants
PubMed: 38933275
DOI: 10.3389/fimmu.2024.1401800 -
Fundamental Research May 2024
PubMed: 38933187
DOI: 10.1016/j.fmre.2024.03.009 -
Aging Cell Jun 2024Alterations in the rate and accuracy of messenger RNA (mRNA) translation are associated with aging and several neurodegenerative disorders, including Alzheimer's disease...
Alterations in the rate and accuracy of messenger RNA (mRNA) translation are associated with aging and several neurodegenerative disorders, including Alzheimer's disease and related tauopathies. We previously reported that error-containing RNA that are normally cleared via nonsense-mediated mRNA decay (NMD), a key RNA surveillance mechanism, are translated in the adult brain of a Drosophila model of tauopathy. In the current study, we find that newly-synthesized peptides and translation machinery accumulate within nuclear envelope invaginations that occur as a consequence of tau pathology, and that the rate of mRNA translation is globally elevated in early stages of disease in adult brains of Drosophila models of tauopathy. Polysome profiling from adult heads of tau transgenic Drosophila reveals the preferential translation of specific mRNA that have been previously linked to neurodegeneration. Unexpectedly, we find that panneuronal elevation of NMD further elevates the global translation rate in tau transgenic Drosophila, as does treatment with rapamycin. As NMD activation and rapamycin both suppress tau-induced neurodegeneration, their shared effect on translation suggests that elevated rates of mRNA translation are an early adaptive mechanism to limit neurodegeneration. Our work provides compelling evidence that tau-induced deficits in NMD reshape the tau translatome by increasing translation of RNA that are normally repressed in healthy cells.
PubMed: 38932463
DOI: 10.1111/acel.14245 -
Vaccines Jun 2024The escalating global healthcare challenge posed by Alzheimer's Disease (AD) and compounded by the lack of effective treatments emphasizes the urgent need for innovative...
The escalating global healthcare challenge posed by Alzheimer's Disease (AD) and compounded by the lack of effective treatments emphasizes the urgent need for innovative approaches to combat this devastating disease. Currently, passive and active immunotherapies remain the most promising strategy for AD. FDA-approved lecanemab significantly reduces Aβ aggregates from the brains of early AD patients administered biweekly with this humanized monoclonal antibody. Although the clinical benefits noted in these trials have been modest, researchers have emphasized the importance of preventive immunotherapy. Importantly, data from immunotherapy studies have shown that antibody concentrations in the periphery of vaccinated people should be sufficient for targeting Aβ in the CNS. To generate relatively high concentrations of antibodies in vaccinated people at risk of AD, we generated a universal vaccine platform, MultiTEP, and, based on it, developed a DNA vaccine, AV-1959D, targeting pathological Aβ, completed IND enabling studies, and initiated a Phase I clinical trial with early AD volunteers. Our current pilot study combined our advanced MultiTEP technology with a novel mRNA approach to develop an mRNA vaccine encapsulated in lipid-based nanoparticles (LNPs), AV-1959LR. Here, we report our initial findings on the immunogenicity of 1959LR in mice and non-human primates, comparing it with the immunogenicity of its DNA counterpart, AV-1959D.
PubMed: 38932388
DOI: 10.3390/vaccines12060659 -
Pharmaceutics Jun 2024In the treatment of experimental neurodegeneration with disaccharide trehalose, various regimens are used, predominantly a 2% solution, drunk for several weeks. We...
In the treatment of experimental neurodegeneration with disaccharide trehalose, various regimens are used, predominantly a 2% solution, drunk for several weeks. We studied the effects of different regimens of dietary trehalose treatment in an amyloid-β (Aβ) 25-35-induced murine model of Alzheimer's disease (AD). Aβ-treated mice received 2% trehalose solution daily, 4% trehalose solution daily (continuous mode) or every other day (intermittent mode), to drink for two weeks. We revealed the dose-dependent effects on autophagy activation in the frontal cortex and hippocampus, and the restoration of behavioral disturbances. A continuous intake of 4% trehalose solution caused the greatest activation of autophagy and the complete recovery of step-through latency in the passive avoidance test that corresponds to associative long-term memory and learning. This regimen also produced an anxiolytic effect in the open field. The effects of all the regimens studied were similar in Aβ load, neuroinflammatory response, and neuronal density in the frontal cortex and hippocampus. Trehalose successfully restored these parameters to the levels of the control group. Thus, high doses of trehalose had increased efficacy towards cognitive impairment in a model of early AD-like pathology. These findings could be taken into account for translational studies and the development of clinical approaches for AD therapy using trehalose.
PubMed: 38931934
DOI: 10.3390/pharmaceutics16060813