Plant‐derived peptides for the improvement of Alzheimer's disease: Production, functions, and mechanisms

Food Frontiers, Journal Year: 2023, Volume and Issue: 4(2), P. 677 - 699

Published: Feb. 22, 2023

Abstract Alzheimer's disease (AD) is a progressive neurodegenerative with an insidious onset that seriously affects human health. Plant‐derived peptides have been found to hinder the development of AD pathologies, which excellent candidate for preventing AD. However, due excessively complicated pathogenesis and fact most studies on activity plant‐derived are single not deep enough, restricted application AD‐prevention (PADPs). This review summarized currently available means obtaining PADPs, in vitro vivo validation protocols, molecular pathways structure–activity relationship between activity, some perspectives current advanced technologies. paper will help develop foundation production exploitation PADPs.

Language: Английский

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Systematic characterization of a non-transgenic Aβ1–42 amyloidosis model: synaptic plasticity and memory deficits in female and male mice

Biology of Sex Differences, Journal Year: 2023, Volume and Issue: 14(1)

Published: Sept. 16, 2023

The amyloid-β (Aβ) cascade is one of the most studied theories linked to AD. In multiple models, Aβ accumulation and dyshomeostasis have shown a key role in AD onset, leading excitatory/inhibitory imbalance, impairments synaptic plasticity oscillatory activity, memory deficits. Despite higher prevalence Alzheimer's disease (AD) women compared men, possible sex difference scarcely explored information from amyloidosis transgenic mice models contradictory. Thus, given lack data regarding early stages female mice, aim this study was systematically characterize effect an intracerebroventricular (icv.) injection Aβ1-42 on hippocampal-dependent memory, associated activity-dependent hippocampal CA1-CA3 synapse, both male mice.To do so, we evaluated long term potentiation (LTP) with ex vivo electrophysiological recordings as well encoding retrieval spatial (working, short- long-term) exploratory habituation memories using Barnes maze object location, or open field tasks, respectively.Aβ1-42 administration impaired all forms work, regardless sex. This displayed long-lasting manner (up 17 days post-injection). LTP inhibited at postsynaptic level, males females, long-term depression (LTD) induced for same prolonged period, which could underlie deficits.In conclusion, our results provide further evidence shifting LTP/LTD threshold due single icv. injection, underly cognitive deficits These functional alterations females validate model sexes, thus offering solid alternative inconsistence models.This focuses investigating how (Aβ), toxic protein (AD), impacts functioning synapses mice.Our primary objective comprehensively understand impact Aβ1–42, specific form Aβ, when introduced into brain's ventricles, focusing processes hippocampus, brain region vital learning memory.Prior research established Aβ's significance decline. However, despite connection between differences required exploration. Furthermore, findings experiments utilizing offered conflicting outcomes. Here, by administering Aβ1–42 assessed tasks. Results were consistent: evident persisting up post-injection.Delving deeper, plasticity, cornerstone memory. Our investigations unveiled disruptions (LTD)—essential processes—in subjected injection.These intriguing underscore Aβ1–42's lasting influence function, emphasizing its AD-related Additionally, highlights potential experimental investigate across differences, promising existing array mouse addressing need more consistent investigative framework.

Language: Английский

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Age-related changes in species-typical behaviours in the 5xFAD mouse model of Alzheimer’s disease from 4 to 16 months of age

Behavioural Brain Research, Journal Year: 2024, Volume and Issue: 465, P. 114970 - 114970

Published: March 24, 2024

Alzheimer's disease (AD) patients show age-related decreases in the ability to perform activities of daily living and decline these is related severity neurobiological deterioration underlying disease. The 5xFAD mouse model AD shows impairments sensory- motor cognitive function, but little known about changes species-typical behaviours that may patients. Therefore, we examined used as indices exploration (rearing) compulsivity (grooming) across six tests anxiety-like behaviour or function female mice from 3-16 months age. Robust rearing were found all after 9 age, although few differences observed grooming. A fine-scale analysis grooming, however, revealed a previously unresolved spatially restricted pattern grooming at 13-16 We then home-cage, impaired nest building ages tested. Lastly, relationship between reduced species typical presentation freezing behaviour, commonly measure memory for conditioned fear. These results showed along with sensory-motor have robust behaviours. help patients, provide useful behavioural phenotypes evaluating pre-clinical efficacy novel therapeutics AD.

Language: Английский

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Physical exercise regulates microglia in health and disease

Frontiers in Neuroscience, Journal Year: 2024, Volume and Issue: 18

Published: June 7, 2024

There is a well-established link between physical activity and brain health. As such, the effectiveness of exercise as therapeutic strategy has been explored in variety neurological contexts. To determine extent to which could be most beneficial under different circumstances, studies are needed uncover underlying mechanisms behind benefits activity. Interest grown understanding how can regulate microglia, resident immune cells central nervous system. Microglia key mediators neuroinflammatory processes play role maintaining homeostasis healthy pathological settings. Here, we explore evidence suggesting that potential microglia various animal models. We emphasize areas where future research contribute uncovering engaging exercise.

Language: Английский

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A functional aged human iPSC‐cortical neuron model recapitulates Alzheimer's disease, senescence, and the response to therapeutics

Alzheimer s & Dementia, Journal Year: 2024, Volume and Issue: 20(9), P. 5940 - 5960

Published: July 30, 2024

Abstract INTRODUCTION The degeneration of cortical layers is associated with cognitive decline in Alzheimer's disease (AD). Current therapies for AD are not disease‐modifying, and, despite substantial efforts, research and development has faced formidable challenges. In addition, cellular senescence emerged as a significant contributor to therapy resistance. METHODS Human iPSC‐derived neurons were cultured on microelectrode arrays measure long‐term potentiation (LTP) noninvasively. Neurons treated pathogenic amyloid‐β (Aβ) analyze response therapeutic molecules. RESULTS Microphysiological recordings revealed Aβ dampened LTP activity accelerated neuronal senescence. Aging secreted inflammatory factors previously detected brain, plasma, cerebral spinal fluid patients, which drugs modulated senescence‐related factors. DISCUSSION This platform measures records molecules real‐time . Efficacy data from similar platforms have been accepted by the FDA neurodegenerative diseases, expediting regulatory submissions. Highlights work developed progerontic model (Aβ)‐driven degeneration. measured correlated function aging biomarkers. driver Molecules rescued but did halt Aβ‐driven Therapeutic secretion neurons.

Language: Английский

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Amyloid-β oligomers trigger sex-dependent inhibition of GIRK channel activity in hippocampal neurons in mice

Science Signaling, Journal Year: 2024, Volume and Issue: 17(856)

Published: Oct. 1, 2024

Alzheimer's disease (AD) is a progressive neurodegenerative characterized by amyloid plaques and cognitive decline, the latter of which thought to be driven soluble oligomeric amyloid-β (oAβ). The dysregulation G protein-gated inwardly rectifying K

Language: Английский

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Editorial: Animal models of Alzheimer's disease and other dementias: past, present, and future

Frontiers in Aging Neuroscience, Journal Year: 2025, Volume and Issue: 16

Published: Jan. 6, 2025

Neurodegenerative diseases, particularly Alzheimer's disease and related dementias (AD/ADRD), represent a significant global health challenge. As of 2019, dementia affected over 57 million individuals worldwide, with projections suggesting this number could exceed 150 by 2050 (GBD 2019Dementia Forecasting Collaborators, 2022). This growing prevalence underscores the need for effective treatments deeper understanding these diseases. Animal models are essential elucidating pathology ADRD, offering valuable insights into mechanisms enabling evaluation therapeutic strategies under controlled conditions. Specifically, transgenic that overexpress human genes linked to familial AD have been instrumental replicating hallmark features AD, including formation extracellular amyloid-β plaques intracellular tau neurofibrillary tangles, closely mirroring neuropathology (Sanchez-Varo, 2022) neuroinflammatory processes associated cerebrovascular dementia. In their study, accelerated ovarian failure was pharmacologically induced in SWDI mice, which express precursor protein vasculotropic mutations (Davis et al., 2004). Their findings revealed dysfunction key components neurovascular unit within hippocampal regions at early stages pathology, perimenopausal period may vulnerable window development dementia.As evolve better capture complex risk factors dementia, stem cell transplantation offer promising alternative address longstanding challenge limited translatability from animal studies clinical applications. issue, Ifediora al. introduce pluripotent (iPSC) as advancement research. By transplanting iPSC-derived neurons, astrocytes, microglia brains, enable study interactions living brain environment, closer approximation conditions than traditional isolated cultures. innovative approach, described authors, holds promise preclinical focused on testing optimizing strategies. However, challenges such long-term aging ensuring stable integration remain chimeric systems. Future emphasizing prolonged observation periods enhanced chronic progressive nature dementias.Recent Through models, authors delve linking elevated blood pressure neurodegeneration. While pathogenic pathways vary among highlight several shared, underlying hypertension-induced damage, demonstrating versatility presented mini review.Beyond hypertension, sleep disturbances also gaining recognition factor (Shi 2018). The rising impact neurodegenerative especially highlights urgent develop improved deepen our neuropathophysiology. Traditional invaluable studying dementia.InNew refined incorporate genetic environmental factorsalong advanced computational approaches -are bridging gap between studies. integrated approach presents future where tools converge new opportunities precise interventions critical public challenge.IM-G, JG-M RM contributed manuscript writing editing. All made substantial intellectual contribution approved it publication.

Language: Английский

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Resilience mechanisms underlying Alzheimer’s disease

Metabolic Brain Disease, Journal Year: 2025, Volume and Issue: 40(1)

Published: Jan. 6, 2025

Language: Английский

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An Overview of Transgenic Mouse Models for the Study of Alzheimer’s Disease

Journal of dementia and Alzheimer's disease, Journal Year: 2025, Volume and Issue: 2(1), P. 2 - 2

Published: Jan. 10, 2025

Alzheimer’s disease (AD) is the most common cause of dementia, and no cure currently available. The β-amyloid cascade AD neurofibrillary tangles are basis current understanding pathogenesis, driving drug investigation other discoveries. Up until now, models have entirely validated hypothesis. must be capable recapitulating critical events this pathology, including plaques tangles. development probably derived from amyloid precursor protein (APP) presenilin 1 (PS1) familial (FAD) mutations, while tangle-like pathology determined by tau mutations. Transgenic mouse struggle to replicate entire spectrum AD, particularly neuronal death stemming pathologies. Furthermore, success these transgenic mice often relies on overexpression APP transgenes enclosing FAD-associated mutations at levels beyond physiological. Ultimate species-specific discrepancies in genome composition between human may hinder accurate recapitulation pathological models. Although none fully mirrors experimental vivo animal provided valuable insights into toxicity overall pathophysiological AD. Therefore, been widely used preclinical evaluation therapeutic strategies played a pivotal role immunotherapies for In review, we sum up main research, whether they mutation-based mice, plus or mice. specific characteristics each model significance their use focusing advantages disadvantages, as well progress made forthcoming challenges replicating neurodegenerative disease, also highlighted.

Language: Английский

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Ventral Midline Hysterectomy, Ovariectomy, and Ovariohysterectomy in Mus Musculus: A Surgical Protocol

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Feb. 24, 2025

Mice (Mus musculus) are one of the most commonly used animal species in basic science and translational research worldwide. Ovariectomy hysterectomy frequently employed to explore systemic effects sex-hormone axis other pathological conditions. While several surgical protocols exist for dorsal ovariectomy rodents, very few address a ventral midline technique, none specific mouse model. Historically, approaches have been considered technically challenging due unique anatomical features, including long, thin uterine horns, fragile salpinges, short ovarian suspensory ligaments, small size. This protocol provides detailed guide performing ovariectomy, hysterectomy, or ovariohysterectomy mice, microsurgical steps required. All procedures were performed using an operative stereomicroscope under 3-5x magnification. The mean weight mice was 24 g (SD = 2 g), with ages ranging from 19 21 weeks. Of 255 surgeries performed, 3 post-operative deaths occurred, resulting attrition rate 1.18%. Post-operatively, all housed groups fresh, paddy husk bedding, no infections wound breakdown observed. Despite their size manipulation vital structures, this procedure is easily reproducible well-tolerated mice.

Language: Английский

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