Alzheimer's Disease Research Articles

Identification of Vascular Genes Differentially Expressed in the Brain of Patients with Alzheimer's Disease.

Alzheimer's disease (AD) plays a prominent role as the most common form of dementia. Moreover, the traditional mechanism of AD does not explain the microvascular damage observed in about 25-30 years between the onset of AD, which results in late application treatment that inhibits or delays neurodegeneration. Our objective was to identify differentially expressed genes in human brain samples associated with vascular disruption in AD. We analyzed 1633 post-mortem brain samples in the GEO to database and, after applying clinical and bioinformatic exclusion criteria, worked with 581 prefrontal and frontal samples. All datasets were analyzed using GEO2R from NCBI. We identified common genes using the Venny tool, and their metabolic relevance associated with AD and the vascular system was analyzed using MetaboAnalyst tools. Our bioinformatic analysis identified PRKCB, MAP2K2, ADCY1, GNA11, GNAQ, PRKACB, KCNMB4, CALD1, and GNAS as potentially involved in AD pathogenesis. These genes are associated with signal transductions, cell death signaling, and cytoskeleton, suggesting potential modulation of cellular physiology, including endoplasmic reticulum and mitochondrial activity. This study generates hypotheses regarding the roles of novel genes over critical pathways relevant to AD and its relation with vascular dysfunction. These findings suggest potential new targets for further investigation into the pathogenesis of dementia and AD.

Phytoactive drugs used in the treatment of Alzheimer's disease and dementia.

The prevalence of Alzheimer's disease and other forms of dementia is increasing worldwide, and finding effective treatments for these conditions is a major public health challenge. Natural bioactive drugs have been identified as a promising source of potential treatments, due to their ability to target multiple pathways and their low toxicity. This paper reviews the current state of research on natural bioactive drugs used in the treatment of Alzheimer's disease and other dementias. The paper summarizes the findings of studies on various natural compounds, including curcumin, resveratrol, caffeine, genistein, quercetin, GinkoBiloba, Withaniasomnifera, Ginseng Brahmi, Giloy, and huperzine, and their effects on cognitive function, neuroinflammation, and amyloid-beta accumulation. In this review, we discuss the mechanism of action involved in the treatment of Alzheimer's disease. The paper also discusses the challenges associated with developing natural bioactive drugs for dementia treatment, including issues related to bioavailability and standardization. Finally, the paper suggests directions for future research in this area, including the need for more rigorous clinical trials and the development of novel delivery systems to improve the efficacy of natural bioactive drugs. Overall, this review highlights the potential of natural bioactive drugs as a promising avenue for the development of safe and effective treatments for Alzheimer's disease and other dementias.

Recent Advancements in the Treatment of Alzheimer's Disease: A Multitarget-directed Ligand Approach.

Alzheimer's disease (AD) is a neurodegenerative disease and one of the leading causes of progressive dementia, affecting 50 million people worldwide. Many pathogenic processes, including amyloid β aggregation, tau hyperphosphorylation, oxidative stress, neuronal death, and deterioration of the function of cholinergic neurons, are associated with its progression. The one-compound-one-target treatment paradigm was unsuccessful in treating AD due to the multifaceted nature of Alzheimer's disease. The recent development of multitarget-directed ligand research has been explored to target the complementary pathways associated with the disease. We aimed to find the key role and progress of MTDLs in treating AD; thus, we searched for the past ten years of literature on "Pub- Med", "ScienceDirect", "ACS" and "Bentham Science" using the keywords neurodegenerative diseases, Alzheimer's disease, and multitarget-directed ligands. The literature was further filtered based on the quality of work and relevance to AD. Thus, this review highlights the current advancement and advantages of multitarget-directed ligands over traditional single-targeted drugs and recent progress in their development to treat AD.

Recent Advancements and SAR Studies of Synthetic Coumarins as MAO-B Inhibitors: An Updated Review.

The oxidative deamination of a wide range of endogenous and exogenous amines is catalyzed by a family of enzymes known as monoamine oxidases (MAOs), which are reliant on flavin-adenine dinucleotides. Numerous neurological conditions, such as Parkinson's disease (PD) and Alzheimer's disease (AD), are significantly correlated with changes in the amounts of biogenic amines in the brain caused by MAO. Hydrogen peroxide, reactive oxygen species, and ammonia, among other toxic consequences of this oxidative breakdown, can harm brain cells' mitochondria and cause oxidative damage. The prime objective of this review article was to highlight and conclude the recent advancements in structure-activity relationships of synthetic derivatives of coumarins for MAO-B inhibition, published in the last five years' research articles. The literature (between 2019 and 2023) was searched from platforms like Science Direct, Google Scholar, PubMed, etc. After going through the literature, we have found a number of coumarin derivatives being synthesized by researchers for the inhibition of MAO-B for the management of diseases associated with the enzyme such as Alzheimer's Disease and Parkinson's Disease. The effect of these coumarin derivatives on the enzyme depends on the substitutions associated with the structure. The structure-activity relationships of the synthetic coumarin derivatives that are popular nowadays have been described and summarized in the current study. The results revealed the updated review on SAR studies of synthetic coumarins as MAO-B inhibitors, specifically for Alzheimer's Disease and Parkinson's Disease. The patents reported on coumarin derivatives as MAO-B inhibitors were also highlighted. Recently, coumarins, a large class of chemicals with both natural and synthetic sources, have drawn a lot of attention because of the vast range of biological actions they have that are linked to neurological problems. Numerous studies have demonstrated that chemically produced and naturally occurring coumarin analogs both exhibited strong MAO-B inhibitory action. Coumarins bind to MAO-B reversibly thereby preventing the breakdown of neurotransmitters like dopamine leading to the inhibition of the enzyme A number of MAO-B blockers have been proven to be efficient therapies for treating neurological diseases like Alzheimer's Disease and Parkinson's Disease. To combat these illnesses, there is still an urgent need to find effective treatment compounds.

Methods to characterize lactate turnover in aging and Alzheimer's disease; The LEAN study

BackgroundThere is evidence that chronic exercise can benefit the brain, but the effects vary markedly between studies. One potential mechanism for exercise-related benefit is the increase in systemic lactate concentration that is well-characterized to occur during exercise. Lactate is known to cross the blood brain barrier and can be used readily as a fuel for neurons. This may be particularly important in Alzheimer's Disease, which is characterized by cerebral hypometabolism. However, little is known about how whole-body lactate metabolism differs between older adults and individuals with cognitive impairment. This information is critical when considering potential differences in responses to exercise in various cognitive diagnosis groups. MethodsHere we describe the use of a “lactate clamp” procedure to adjust blood lactate levels to approximate those achieved during exercise, but while at rest. This trial will compare lactate oxidation between cognitively healthy older adults and cognitively impaired participants. We will further evaluate the effect of acute lactate infusion on cognitive performance. DiscussionThe findings of the study described here, the Lactate for Energy and Neurocognition trial (clinicaltrials.gov # NCT05207397) will add to our understanding of systemic lactate mechanics in cognitively healthy older adults and individuals with Alzheimer's Disease. These findings will be applicable to ongoing exercise trials and to future studies aimed at modulating systemic bioenergetic function in aging and Alzheimer's Disease.

Effect of heatwaves on mortality of Alzheimer's disease and other dementias among elderly aged 60 years and above in China, 2013–2020: a population-based study

BackgroundChina has the largest number of dementia patients in the world, posing a significant health and economic burden. Alzheimer's disease (AD) and other dementia patients face a higher risk of mortality during heatwaves, but relevant studies on this topic have been limited so far. MethodsThe study extracted data from the China Cause of Death Reporting System (CDRS) on deaths of AD and other dementia patients aged 60 years and above between 2013-2020. Using an individual-level, time-stratified, and case-crossover study design, the effects of heatwaves across nine scenarios on dementia mortality were quantified by conditional logistic regression combined with distributed lag non-linear model (DLNM). Additionally, the attributable fractions (AFs) of deaths due to heatwaves were calculated. FindingsA total of 399,036 death cases were reported caused by AD and other dementias during the study period. It was found that heatwaves significantly increased the risk of death among people with AD and other dementias. As the intensities and durations of the heatwaves increased, the lag0-7 cumulative odds ratios (CORs) of mortality increased progressively from 1·140 (95% CI: 1·118, 1·163) under the mildest heatwave to 1·459 (95% CI: 1·403, 1·518) under the most severe one, across nine heatwave scenarios examined. Additionally, under specific heatwave scenarios, sex and regions modified the mortality risk, but no significant age differences were observed. The AFs of AD and other dementia mortality due to milder heatwaves were lower compared to more severe heatwaves, ranging from 12·281% (95% CI: 10·555%, 14·015%) to 31·460% (95% CI: 28·724%, 34·124%). InterpretationThe study provided critical insights into the substantial increase in heatwave-related mortality among AD and other dementia patients during and after heatwave events. The results from our quantitative analyses will provide needed scientific evidence for policymakers and practitioners to develop relevant policies and guidelines to protect the health and well-beings of vulnerable populations in future in the context of both seasonal changes and long-term climate change. FundingThis work was supported by the Project of Prevention and Intervention on Major Diseases for Elderly in China, NCNCD [00240201307], the National Key Research and Development Program of China [2022YFC2602301, 2023YFC2308703] and the Science and Technology Fundamental Resources Investigation Program of China [2017FY101201].

Relationship between MRI brain-age heterogeneity, cognition, genetics and Alzheimer’s disease neuropathology

Brain ageing is highly heterogeneous, as it is driven by a variety of normal and neuropathological processes. These processes may differentially affect structural and functional brain ageing across individuals, with more pronounced ageing (older brain age) during midlife being indicative of later development of dementia. Here, we examined whether brain-ageing heterogeneity in unimpaired older adults related to neurodegeneration, different cognitive trajectories, genetic and amyloid-beta (Aβ) profiles, and to predicted progression to Alzheimer's disease (AD). Functional and structural brain age measures were obtained for resting-state functional MRI and structural MRI, respectively, in 3460 cognitively normal individuals across an age range spanning 42-85 years. Participants were categorised into four groups based on the difference between their chronological and predicted age in each modality: advanced age in both (n=291), resilient in both (n=260) or advanced in one/resilient in the other (n=163/153). With the resilient group as the reference, brain-age groups were compared across neuroimaging features of neuropathology (white matter hyperintensity volume, neuronal loss measured with Neurite Orientation Dispersion and Density Imaging, AD-specific atrophy patterns measured with the Spatial Patterns of Abnormality for Recognition of Early Alzheimer's Disease index, amyloid burden using amyloid positron emission tomography (PET), progression to mild cognitive impairment and baseline and longitudinal cognitive measures (trail making task, mini mental state examination, digit symbol substitution task). Individuals with advanced structural and functional brain-ages had more features indicative of neurodegeneration and they had poor cognition. Individuals with a resilient brain-age in both modalities had a genetic variant that has been shown to be associated with age of onset of AD. Mixed brain-age was associated with selective cognitive deficits. The advanced group displayed evidence of increased atrophy across all neuroimaging features that was not found in either of the mixed groups. This is in line with biomarkers of preclinical AD and cerebrovascular disease. These findings suggest that the variation in structural and functional brain ageing across individuals reflects the degree of underlying neuropathological processes and may indicate the propensity to develop dementia in later life. The National Institute on Aging, the National Institutes of Health, the Swiss National Science Foundation, the Kaiser Foundation Research Institute and the National Heart, Lung, and Blood Institute.

Machine learning reveals prominent spontaneous behavioral changes and treatment efficacy in humanized and transgenic Alzheimer's disease models

Computer-vision and machine-learning (ML) approaches are being developed to provide scalable, unbiased, and sensitive methods to assess mouse behavior. Here, we used the ML-based variational animalmotion embedding (VAME) segmentation platform to assess spontaneous behavior in humanized App knockin and transgenic APP models of Alzheimer's disease (AD) and to test the role of AD-related neuroinflammation in these behavioral manifestations. We found marked alterations in spontaneous behaviorin AppNL-G-F and 5xFAD mice, including age-dependent changes in motif utilization, disorganized behavioral sequences, increased transitions, and randomness. Notably, blocking fibrinogen-microglia interactions in 5xFAD-Fggγ390-396A mice largely prevented spontaneous behavioral alterations, indicating akey role for neuroinflammation. Thus, AD-related spontaneous behavioral alterations are prominent in knockin and transgenic models and sensitive to therapeutic interventions. VAME outcomes had higherspecificity and sensitivity than conventional behavioral outcomes. We conclude that spontaneous behavior effectively captures age- and sex-dependent disease manifestations and treatment efficacy in AD models.

Sphingosine 1-phosphate receptor subtype 1 (S1P1) activity in the course of Alzheimer's disease

Some specific lipid molecules in the brain act as signaling molecules, neurotransmitters, or neuromodulators, by binding to specific G protein-coupled receptors (GPCR) for neurolipids. One such receptor, sphingosine 1-phosphate receptor subtype 1 (S1P1), is coupled to Gi/o proteins and is involved in cell proliferation, growth, and neuroprotection. S1P1 constitutes an interesting target for neurodegenerative diseases like multiple sclerosis and Alzheimer's disease (AD), in which changes in the sphingolipid metabolism have been observed. This study analyzes S1P1 receptor-mediated activity in healthy brains and during AD progression using postmortem samples from controls and patients at different Braak's stages. Additionally, the distribution of S1P1 receptor activity in human brains is compared to that in commonly used rodent models, rats and mice, through functional autoradiography, measuring [35S]GTPγS binding stimulated by the S1P1 receptor selective agonist CYM-5442 to obtain the distribution of functional activity of S1P1 receptors.S1P1 receptor-mediated activity, along with that of the cannabinoid CB1 receptor, is one of the highest recorded for any GPCR in many gray matter areas of the brain, reaching maximum values in the cerebellar cortex, specific areas of the hippocampus and the basal forebrain. S1P1 signaling is crucial in areas that regulate learning, memory, motor control, and nociception, such as the basal forebrain and basal ganglia. In AD, S1P1 receptor activity is increased in the inner layers of the frontal cortex and underlying cortical white matter at early stages, but decreases in the hippocampus in advanced stages, indicating ongoing brain impairment. Importantly, we identified significant correlations between S1P1 receptor activity and Braak stages, suggesting that S1P1 receptor dysfunction is associated to disease progression, particularly in memory-related regions. The S1P signaling via S1P1 receptor is a promising neurological target due to its role in key neurophysiological functions and its potential to modify the progression of neurodegenerative diseases. Finally, rats are suggested as a preferred experimental model for studying S1P1 receptor-mediated responses in the human brain.

Epigenetic Mechanisms of Aluminum-Induced Neurotoxicity and Alzheimer's Disease: A Focus on Non-Coding RNAs.

Aluminum (Al) is known to induce neurotoxic effects, potentially contributing to Alzheimer's disease (AD) pathogenesis. Recent studies suggest that epigenetic modification may contribute to Al neurotoxicity, although the mechanisms are still debatable. Therefore, the objective of the present study was to summarize existing data on the involvement of epigenetic mechanisms in Al-induced neurotoxicity, especially AD-type pathology. Existing data demonstrate that Al exposure induces disruption in DNA methylation, histone modifications, and non-coding RNA expression in brains. Alterations in DNA methylation following Al exposure were shown to be mediated by changes in expression and activity of DNA methyltransferases (DNMTs) and ten-eleven translocation proteins (TETs). Al exposure was shown to reduce histone acetylation by up-regulating expression of histone deacetylases (HDACs) and impair histone methylation, ultimately contributing to down-regulation of brain-derived neurotrophic factor (BDNF) expression and activation of nuclear factor κB (NF-κB) signaling. Neurotoxic effects of Al exposure were also associated with aberrant expression of non-coding RNAs, especially microRNAs (miR). Al-induced patterns of miR expression were involved in development of AD-type pathology by increasing amyloid β (Aβ) production through up-regulation of Aβ precursor protein (APP) and β secretase (BACE1) expression (down-regulation of miR-29a/b, miR-101, miR-124, and Let-7c expression), increasing in neuroinflammation through NF-κB signaling (up-regulation of miR-9, miR-125b, miR-128, and 146a), as well as modulating other signaling pathways. Furthermore, reduced global DNA methylation, altered histone modification, and aberrant miRNA expression were associated with cognitive decline in Al-exposed subjects. However, further studies are required to evaluate the contribution of epigenetic mechanisms to Al-induced neurotoxicity and/or AD development.

Getting sincere and efficient support: A grounded theory study of older spousal caregivers of people with alzheimer's disease

Despite the importance of supporting older spousal caregivers (OSCs) of people with Alzheimer's Disease (PWAD), little evidence is available about the process of its occurrence in Middle Eastern countries, such as Iran. Understanding this process will help support more effectively. This study explored the support process for OSCs of PWAD using the grounded theory approach of Corbin and Strauss (2015). A total of 16 participants (10 caregivers, six formal and informal resources) were recruited using purposive and theoretical sampling methods, and in-depth interviews were conducted with them. Getting sincere and efficient support was the core category and was achieved through four strategies, which were thoughtful support-seeking, informal support-getting, formal seasonal support-getting, and informal support-devoting. Despite OSCs' vital need for multiple support, specific factors and conditions impair the support process. Healthcare providers and policymakers can use the results to make informed decisions and provide more practical support for these older caregivers.

Targeting Insulin- and Calcium-related Pathways for Potential Treatments for Alzheimer's Disease and Diabetes

: Alzheimer's disease and diabetes are common disorders among the elderly population and have emerged as a major health concern. Both diseases pose considerable risks to one another. Diabetics have a significantly increased probability of getting Alzheimer's disease throughout their lifetime. These diseases are linked because, both share common risk factors such as impaired carbohydrate metabolism, insulin resistance, oxidative stress, inflammatory response, mitochondrial dysfunction, and amyloidosis. Insulin is a vital hormone responsible for bringing extremely high glucose levels back to normal and its receptors available in the hippocampus help in enhancing cognitive function. Insulin resistance consequently serves as a link between both diabetes and AD. Similarly, amylin is another hormone secreted by the pancreas along with insulin. During diabetes, amylin gets oligomerized and forms a neurotoxic complex with Aβ inside the brain, which causes AD to develop. Along with these, another main mechanism influencing AD development is Ca2+ dyshomeostasis. Insulin production from the pancreas is generally aided by Ca2+, but in excess, it can cause dysregulation of many signaling pathways such as CaMKK2, CAMP, CREB, MAPK, STIM\Orai, etc. which can ultimately result in the pathogenesis of AD in diabetic people. In this review, we discussed in detail the pathogenesis of AD associated with diabetes and the mechanisms initiating their progression.

Dignity in people with dementia: A concept analysis.

Background: Dignity, an abstract and complex concept, is an essential part of humanity and an underlying guiding principle in healthcare. Previous literature indicates dignity is compromised in people with dementia (PwD), but those PwD maintain the capacity to live with dignity with appropriate external support. Alzheimer's disease and related dementias (ADRDs) lead to progressive functional decline and increased vulnerability and dependence, leading to heightened risks of PwD receiving inappropriate or insufficient care that diminishes dignity. Considering the increased disease prevalence and the continuously escalating costs of dementia care, establishing a productive value-based guideline may prevent suffering, maximize dignity, and thus promote quality of life (QoL).Aim: The goal of this project is to identify actionable targets for integrating dignity harmoniously and practically into care planning and management for PwD.Research Design: We conducted a concept analysis using Walker and Avant's eight-step process. A comprehensive literature search was conducted (PubMed and CINAHL) with the keywords "dignity," "dementia," "Alzheimer's disease," and "dementia care."Results: A total of 42 out of 4910 publications were included. The concept of dignity in PwD is operationalized as the promotion of worthiness and the accordance of respect that allows the presence and expression of a person's sense of self, regardless of physical, mental, or cognitive health. The concept has two subdimensions: absolute dignity which encompasses the inherent self and relative dignity characterized by its dynamic reflective nature. Worthiness and respect are the two main attributes, while autonomy is an underlying component of dignity. Specific antecedents of dignity in PwD are empowerment, non-maleficence, and adaptive environmental scaffolding. As a consequence of facilitating dignity in PwD, QoL may be enhanced.Conclusion: As a foundational and necessary humanistic value, incorporating dignity into dementia care can lead to efficient and effective care that optimizes QoL in PwD throughout their disease progression.

Detection and staging of Alzheimer's disease by plasma pTau217 on a high throughput immunoassay platform

Plasma phospho-tau 217 (pTau217) assays can accurately detect Alzheimer's disease (AD) pathology, but clinical application is limited by the need for specialised equipment. This study tests the performance of a plasma pTau217 assay performed on the Lumipulse-G® platform, that is in widespread clinical use, for selecting patients for therapy based on β-amyloid (Aβ) status and tau staging. Participants included 388 individuals with 18F-NAV4694 Aβ-PET and 18F-MK6240 tau-PET. Association of pTau217 with PET was examined using Spearman's correlation. Discriminative performance for Aβ and tau PET status as well as tau staging was assessed using Receiver Operating Characteristic analysis. Plasma pTau217 had a high correlation with both Aβ Centiloid (r=0.76) and tau SUVRmeta-temporal (r=0.78). Area under curve (AUC) was 0.93 for Aβ- vs Aβ+ and 0.94 for tau- vs tau+. Applying one threshold (Youden's index), pTau217 was 87% accurate in classification of participants to Aβ- vs Aβ+. Applying two thresholds to classify participants into Low, Indeterminate, and High zones, 17.8% had Indeterminate results and among Low/High zone participants, 92% were correctly classified as Aβ- or Aβ+. The assay accurately discriminated moderate/high neocortical tau from no tau or tau limited to mesial-temporal lobe (AUC 0.97) and high neocortical tau from all others (AUC 0.94). Plasma pTau217, measured by the widely-available, fully-automated Lumipulse®, was a strong predictor of both Aβ and tau PET status and demonstrated strong predictive power in identifying individuals likely to benefit the most from anti-Aβ treatments. NHMRC grants 1132604, 1140853, 1152623 and AbbVie.

Pharmacological Approaches and Herbal Interventions for Alzheimer's Disease

Abstract: This comprehensive review extensively examines the utilization of herbal remedies and pharmacological techniques for managing Alzheimer's disease (AD). It delves deeply into the active constituents and modes of operation of diverse herbal medications such as Withania somnifera, Bacopa monnieri, Ginkgo biloba, and Curcuma longa, emphasizing their qualities in reducing inflammation, acting as antioxidants, and safeguarding neural tissue. Additionally, it assesses conventional pharmaceuticals like cholinesterase inhibitors (Donepezil, rivastigmine) and memantine, investigating their mechanisms of action and potential adverse effects. The study also encompasses non-pharmacological therapies like interventions aimed at cognition, physical exercise, and methods of stimulating the brain, all of which exhibit potential in enhancing cognitive capacity and neural adaptability. Furthermore, it delves into the amalgamation of therapies to tackle numerous facets of AD pathology. In essence, this review furnishes valuable insights into alternative strategies for managing AD, underscoring the potential of herbal interventions in enhancing cognitive function and addressing the underlying issues of AD. Additionally, it presents a fresh avenue for exploring the collaborative impacts of combining conventional pharmaceuticals with herbal remedies.

Targeting GM2 Ganglioside Accumulation in Dementia: Current Therapeutic Approaches and Future Directions.

Dementia in neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), and dementia with Lewy bodies (DLB) is a progressive neurological condition affecting millions worldwide. The amphiphilic molecule GM2 gangliosides are abundant in the human brain and play important roles in neuronal development, intercellular recognition, myelin stabilization, and signal transduction. GM2 ganglioside's degradation requires hexosaminidase A (HexA), a heterodimer composed of an α subunit encoded by HEXA and a β subunit encoded by HEXB. The hydrolysis of GM2 also requires a non-enzymatic protein, the GM2 activator protein (GM2-AP), encoded by GM2A. Pathogenic mutations of HEXA, HEXB, and GM2A are responsible for autosomal recessive diseases known as GM2 gangliosidosis, caused by the excessive intralysosomal accumulation of GM2 gangliosides. In AD, PD and DLB, GM2 ganglioside accumulation is reported to facilitate Aβ and α-synuclein aggregation into toxic oligomers and plaques through activation of downstream signaling pathways, such as protein kinase C (PKC) and oxidative stress factors. This review explored the potential role of GM2 ganglioside alteration in toxic protein aggregations and its related signaling pathways leading to neurodegenerative diseases. Further review explored potential therapeutic approaches, which include synthetic and phytomolecules targeting GM2 ganglioside accumulation in the brain, holding a promise for providing new and effective management for dementia.

Astrocytes and Memory: Implications for the Treatment of Memory-related Disorders.

Memory refers to the imprint accumulated in the brain by life experiences and represents the basis for humans to engage in advanced psychological activities such as thinking and imagination. Previously, research activities focused on memory have always targeted neurons. However, in addition to neurons, astrocytes are also involved in the encoding, consolidation, and extinction of memory. In particular, astrocytes are known to affect the recruitment and function of neurons at the level of local synapses and brain networks. Moreover, the involvement of astrocytes in memory and memory-related disorders, especially in Alzheimer's disease (AD) and post-traumatic stress disorder (PTSD), has been investigated extensively. In this review, we describe the unique contributions of astrocytes to synaptic plasticity and neuronal networks and discuss the role of astrocytes in different types of memory processing. In addition, we also explore the roles of astrocytes in the pathogenesis of memory-related disorders, such as AD, brain aging, PTSD and addiction, thus suggesting that targeting astrocytes may represent a potential strategy to treat memory-related neurological diseases. In conclusion, this review emphasizes that thinking from the perspective of astrocytes will provide new ideas for the diagnosis and therapy of memory-related neurological disorders.

Recombinant Antibody Fragments for Neurological Disorders: An Update.

Recombinant antibody fragments are promising alternatives to full-length immunoglobulins, creating big opportunities for the pharmaceutical industry. Nowadays, antibody fragments such as antigen-binding fragments (Fab), single-chain fragment variable (scFv), single-domain antibodies (sdAbs), and bispecific antibodies (bsAbs) are being evaluated as diagnostics or therapeutics in preclinical models and in clinical trials. Immunotherapy approaches, including passive transfer of protective antibodies, have shown therapeutic efficacy in several animal models of Alzheimer's disease (AD), Parkinson's disease (PD), frontotemporal dementia (FTD), Huntington's disease (HD), transmissible spongiform encephalopathies (TSEs) and multiple sclerosis (MS). There are various antibodies approved by the Food and Drug Administration (FDA) for treating multiple sclerosis and two amyloid beta-specific humanized antibodies, Aducanumab and Lecanemab, for AD. Our previous review summarized data on recombinant antibodies evaluated in pre-clinical models for immunotherapy of neurodegenerative diseases. Here, we explore recent studies in this fascinating research field, give an update on new preventive and therapeutic applications of recombinant antibody fragments for neurological disorders and discuss the potential of antibody fragments for developing novel approaches for crossing the blood-brain barrier (BBB) and targeting cells and molecules of interest in the brain.

Caenorhabditis elegans as an Outstanding Model to Explore Flavonoids Under Stress Conditions

Abstract: Plants produce promising chemicals called secondary metabolites in response to stress, which protect against oxidative damage in both plants and humans. Reactive oxygen species (ROS) levels combined with an imbalance in the antioxidant responses can trigger oxidative stress that is related to many conditions such as Alzheimer's disease, diabetes, and cancer. One way to counteract or avoid the stress excess is by flavonoid administration, a class of plant metabolites with a consistent antioxidant action and the ability to inactivate the free radical excess. The mechanisms, as well as the benefits and toxicity of antioxidant products, can be tested in alternative animal models. The mechanisms, as well as the benefits and toxicity of antioxidant products, can be tested in alternative animal models. In this review, we explored how Caenorhabditis elegans, a nematode with high genetic similarity to human genes and the antioxidant response pathway conserved, can be considered an attractive model organism for testing flavonoid compounds. Here, we emphasize the crucial results regarding C. elegans and the flavonoid quercetin, focusing on oxidative stress and aging investigations. Also, this review highlights the quercetin benefits in C. elegans lifespan, healthspan, neurodegeneration, and impacts on insulin/IGF-1 signaling (IIS).

Neuroprotection and mechanisms of ginsenosides in nervous system diseases: Progress and perspectives.

Ginsenosides are the primary component discernible from ginseng, including Rb1, Rb2, Rd, Rg1, Rg2, and compound K, and so forth. They have been shown to have multiple pharmacological activities. In recent years, more and more studies have been devoted to the neuroprotection of various ginsenosides against neurological diseases and their potential mechanisms. This paper comprehensively summarizes and reviews the neuroprotective effects of various ginsenosides on neurological diseases, especially acute and chronic neurodegenerative diseases, and their mechanisms, as well as their potential therapeutic applications to promote neuroprotection in disease prevention, treatment, and prognosis. Briefly, ginsenosides exert effective neuroprotective effects on neurological conditions, including stroke, Alzheimer's disease, Parkinson's disease, and brain/spinal cord injuries through a variety of molecular mechanisms, including anti-inflammatory, antioxidant, and anti-apoptotic. Among them, some signaling pathways play important roles in related processes, such as PI3K/Akt, TLR4/NF-κB, ROS/TXNIP/NLRP3, HO-1/Nrf2, Wnt/β-catenin, and Ca2+ pathway. In conclusion, the present study reviews the research progress on the neuroprotective effects of ginsenosides in the last decade, with the aim of furnishing essential theoretical underpinning and effective references for further research and exploration of the multiple medicinal values of Chinese herbal medicines and their small molecule compounds, including ginseng and panax ginseng. Because there is less evidence in the existing clinical studies, future research should be focused on clinical trials in order to truly reflect the clinical value of various ginsenosides for the benefit of patients.