Search

Alzheimer's disease (AD) is the most predominant cause of dementia, considered a progressive decline in cognitive function that ultimately leads to death. AD has posed a substantial challenge in the records of medical science over the past century, representing a predominant etiology of dementia with a high prevalence rate. Neuroinflammation is a common characteristic of various central nervous system (CNS) pathologies like AD, primarily mediated by specialized brain immune and inflammatory cells, such as astrocytes and microglia. The present study aims to elucidate the potential mechanism of physcion that mitigates LPS-induced gliosis and assesses oxidative stress in mice. Physcion reduced the reactivity of Iba-1- and GFAP-positive cells and decreased the level of inflammatory cytokines like TNF-α and IL-1β. Physcion also reversed the effect of LPS-induced oxidative stress by upregulating the expression of Nrf2 and HO-1. Moreover, physcion treatment reversed LPS-induced synaptic disorder by increasing the level of presynaptic protein SNAP-23 and postsynaptic protein PSD-95. Our findings may provide a contemporary theoretical framework for clinical investigations aimed at examining the pathogenic mechanisms and therapeutic approaches for neuroinflammation and AD. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that comprises amyloid-beta protein (Aβ) as a main component of neuritic plaques. Its deposition is considered a trigger for AD pathogenesis, progression, and the clinical symptoms of cognitive impairment. Some distinct pathological features of AD include phosphorylation of tau protein, oxidative stress, and mitochondrial dysfunction. These pathological consequences tend to produce reactive oxygen species (ROS), resulting in the dysregulation of various signaling pathways of neuroinflammation and neurodegeneration. The relationship between the Aβ cascade and oxidative stress in AD pathogenesis is like a "chicken and egg" story, with the etiology of the disease regarding these two factors remaining a question of "which comes first." However, in this review, we have tried our best to clarify the interconnection between these two mechanisms and to show the precise cause-and-effect relationship. Based on the above hallmarks of AD, several therapeutic strategies using natural antioxidants, monoclonal antibodies, and vaccines are employed as anti-Aβ therapy to decrease ROS, Aβ burden, chronic neuroinflammation, and synaptic failure. These natural antioxidants and immunotherapeutics have demonstrated significant neuroprotective effects and symptomatic relief in various in vitro and in vivo models, as well as in clinical trials for AD. However, none of them have received final approval to enter the drug market for mitigating AD. In this review, we extensively elaborate on the pitfalls, assurances, and important crosstalk between oxidative stress and Aβ concerning current anti-Aβ therapy. Additionally, we discuss future strategies for the development of more Aβ-targeted approaches and the optimization of AD treatment and mitigation. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD), is a progressive neurodegenerative disorder that involves the deposition of β-amyloid plaques and the clinical symptoms of confusion, memory loss, and cognitive dysfunction. Despite enormous progress in the field, no curative treatment is available. Therefore, the current study was designed to determine the neuroprotective effects of N-methyl-(2S, 4R)-Trans-4-hydroxy-L-proline (NMP) obtained from Sideroxylon obtusifolium, a Brazilian folk medicine with anti-inflammatory and anti-oxidative properties. Here, for the first time, we explored the neuroprotective role of NMP in the Aβ1–42-injected mouse model of AD. After acclimatization, a single intracerebroventricular injection of Aβ1–42 (5 µL/5 min/mouse) in C57BL/6N mice induced significant amyloidogenesis, reactive gliosis, oxidative stress, neuroinflammation, and synaptic and memory deficits. However, an intraperitoneal injection of NMP at a dose of (50 mg/kg/day) for three consecutive weeks remarkably decreased beta secretase1 (BACE-1) and Aβ, activated the astrocyte and microglia expression level as well as downstream inflammatory mediators such as pNF-ĸB, TNF-α, and IL-1β. NPM also strongly attenuated oxidative stress, as evaluated by the expression level of NRF2/HO-1, and synaptic failure, by improving the level of both the presynaptic (SNAP-25 and SYN) and postsynaptic (PSD-95 and SNAP-23) regions of the synapses in the cortexes and hippocampi of the Aβ1–42-injected mice, contributing to cognitive improvement in AD and improving the behavioral deficits displayed in the Morris water maze and Y-maze. Overall, our data suggest that NMP provides potent multifactorial effects, including the inhibition of amyloid plaques, oxidative stress, neuroinflammation, and cognitive deficits. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is the most common neurodegenerative disease illustrated by neuronal dysfunctions, leading to memory weaknesses and personality changes mostly in the aged population worldwide. The exact cause of AD is unclear, but numerous studies have addressed the involvement of oxidative stress (OS), induced by reactive oxygen species (ROS), to be one of the leading causes in developing AD. OS dysregulates the cellular homeostasis, causing abnormal protein and lipid metabolism. Nutrition plays a pivotal role in modulating the antioxidant system and decreases the neuronal ROS level, thus playing an important therapeutic role in neurodegenerative diseases, especially in AD. Hence, medicinal herbs and their extracts have received global attention as a commercial source of antioxidants Lupeol. Lupeol is a pentacyclic triterpenoid and has many biological functions. It is available in fruits, vegetables, and medicinal plants. It has shown effective antioxidant and anti-inflammatory properties, and higher blood–brain barrier permeability. Also, the binding and inhibitory potentials of Lupeol have been investigated and proved to be effective against certain receptor proteins and enzymes in AD studies by computational molecular docking approaches. Therefore, AD-related research has gained interest in investigating the therapeutic effects of Lupeol. However, despite its beneficial effects in AD, there is still a lack of research in Lupeol. Hence, we compiled in this analysis all preclinical research that looked at Lupeol as an antioxidant and anti-inflammatory agent for AD. [ABSTRACT FROM AUTHOR]

Trolox is a potent antioxidant and a water-soluble analog of vitamin E. It has been used in scientific studies to examine oxidative stress and its impact on biological systems. Trolox has been shown to have a neuroprotective effect against ischemia and IL-1β-mediated neurodegeneration. In this study, we investigated the potential protective mechanisms of Trolox against a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease mouse model. Western blotting, immunofluorescence staining, and ROS/LPO assays were performed to investigate the role of trolox against neuroinflammation, the oxidative stress mediated by MPTP in the Parkinson's disease (PD) mouse model (wild-type mice (C57BL/6N), eight weeks old, average body weight 25–30 g). Our study showed that MPTP increased the expression of α-synuclein, decreased tyrosine hydroxylase (TH) and dopamine transporter (DAT) levels in the striatum and substantia nigra pars compacta (SNpc), and impaired motor function. However, Trolox treatment significantly reversed these PD-like pathologies. Furthermore, Trolox treatment reduced oxidative stress by increasing the expression of nuclear factor erythroid-2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). Lastly, Trolox treatment inhibited the activated astrocytes (GFAP) and microglia (Iba-1), also reducing phosphorylated nuclear factor-κB, (p-NF-κB) and tumor necrosis factor-alpha (TNF-α) in the PD mouse brain. Overall, our study demonstrated that Trolox may exert neuroprotection on dopaminergic neurons against MPTP-induced oxidative stress, neuroinflammation, motor dysfunction, and neurodegeneration. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a degenerative brain disease that affects millions of people worldwide. It is caused by abnormalities in cholinergic neurons, oxidative stress, and inflammatory cascades. The illness is accompanied by personality changes, memory issues, and dementia. Metabolic signaling pathways help with fundamental processes like DNA replication and RNA transcription. Being adaptable is essential for both surviving and treating illness. The body's metabolic signaling depends on adipokines, including adiponectin (APN) and other adipokines secreted by adipose tissues. Energy homeostasis is balanced by adipokines, and nutrients. Overconsumption of nutrients messes with irregular signaling of adipokines, such as APN in both peripheral and brain which leads to neurodegeneration, such as AD. Despite the failure of traditional treatments like memantine and cholinesterase inhibitors, natural plant bioactive substances like Osmotin (OSM) have been given a focus as potential therapeutics due to their antioxidant properties, better blood brain barrier (BBB) permeability, excellent cell viability, and especially nanoparticle approaches. The review highlights the published preclinical literature regarding the role of OSM in AD pathology while there is a need for more research to investigate the hidden therapeutic potential of OSM which may open a new gateway and further strengthen its healing role in the pathogenesis of neurodegeneration, especially AD. • Metabolic homeostasis plays an important role in Periphery and CNS. • Adiponectin (APN) metabolic signaling is crucial for homeostatic balance in Periphery and CNS. • Alzheimer's Disease (AD) is closely related to metabolic abnormalities. • APN plays a leading role in metabolic syndrome (MetS) and AD Pathogenesis. • Osmotin is an emerging therapeutic approach for AD pathology. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is a progressive neurodegenerative disorder pathologically characterized by the deposition of amyloid beta (Aβ) plaques and neurofibrillary tangles (NFTs) in the brain. The accumulation of these aggregated proteins causes memory and synaptic dysfunction, neuroinflammation, and oxidative stress. This research study is significant as it aims to assess the neuroprotective properties of vitamin E (VE) analog Trolox in an Aβ 1 - 42 -induced AD mouse model. Aβ 1 - 42 5μL/5min/mouse was injected intracerebroventricularly (i.c.v.) into wild-type adult mice brain to induce AD-like neurotoxicity. For biochemical analysis, Western blotting and confocal microscopy were performed. Remarkably, intraperitoneal (i.p.) treatment of Trolox (30 mg/kg/mouse for 2 weeks) reduced the AD pathology by reducing the expression of Aβ, phosphorylated tau (p-tau), and β-site amyloid precursor protein cleaving enzyme1 (BACE1) in both cortex and hippocampus regions of mice brain. Furthermore, Trolox-treatment decreased neuroinflammation by inhibiting Toll-like receptor 4 (TLR4), phosphorylated nuclear factor-κB (pNF-κB) and interleukin-1β (IL-1β), and other inflammatory biomarkers of glial cells [ionized calcium-binding adaptor molecule 1 (Iba1) and glial fibrillary acidic protein (GFAP)]. Moreover, Trolox reduced oxidative stress by enhancing the expression of nuclear factor erythroid-related factor 2 (NRF2) and heme oxygenase 1 (HO1). Similarly, Trolox-induced synaptic markers, including synaptosomal associated protein 23 (SNAP23), synaptophysin (SYN), and post-synaptic density protein 95 (PSD-95), and memory functions in AD mice. Our findings could provide a useful and novel strategy for investigating new medications to treat AD-associated neurodegenerative diseases., Competing Interests: MOK was employed by Alz-Dementia Korea Co. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Tahir, Kang, Park, Ali, Choe, Park and Kim.)

Intense neuroinflammation contributes to neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease. Lipopolysaccharides (LPSs) are an integral part of the cell wall of Gram-negative bacteria that act as pathogen-associated molecular patterns (PAMPs) and potentially activate the central nervous system's (CNS) immune system. Microglial cells are the local macrophages of the CNS and have the potential to induce and control neuroinflammation. This study aims to evaluate the anti-inflammatory and antioxidant effect of kojic acid against the toxic effects of LPSs, such as neuroinflammation-induced neurodegeneration and cognitive decline. The C57BL/6N mice were subjected to LPS injection for 2 weeks on alternate days (each mouse received 0.25 mg/kg/i.p. for a total of seven doses), and kojic acid was administered orally for 3 weeks consecutively (50 mg/kg/mouse, p. o). Bacterial endotoxins, or LPSs, are directly attached to TLR4 surface receptors of microglia and astrocytes and alter the cellular metabolism of immune cells. Intraperitoneal injection of LPS triggers the toll-like receptor 4 (TLR4), phospho-nuclear factor kappa B (p-NFκB), and phospho-c-Jun n-terminal kinase (p-JNK) protein expressions in the LPS-treated group, but these expression levels were significantly downregulated in the LPS + KA-treated mice brains. Prolong neuroinflammation leads to the generation of reactive oxygen species (ROS) followed by a decrease in nuclear factor erythroid-2-related factor 2 (Nrf2) and the enzyme hemeoxygenase 1 (HO-1) expression in LPS-subjected mouse brains. Interestingly, the levels of both Nrf-2 and HO-1 increased in the LPS + KA-treated mice group. In addition, kojic acid inhibited LPS-induced TNF-α and IL-1β production in mouse brains. These results indicated that kojic acid may suppress LPS-induced neuroinflammation and oxidative stress in male wild-type mice brains (in both the cortex and the hippocampus) by regulating the TLR4/NF-κB signaling pathway., Competing Interests: Author MK was employed by Alz-Dementia Korea Co. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Ali, Choe, Park, Ahmad, Park, Kang, Park and Kim.)

Neuroinflammation includes the activation of immune glial cells in the central nervous system, release pro-inflammatory cytokines, which disrupt normal neural function and contribute to various neurological disorders, including Alzheimer's disease (AD), Parkinson's disease, multiple sclerosis, and stroke. AD is characterized by various factors including amyloidogenesis, synaptic dysfunction, memory impairment and neuroinflammation. Lipopolysaccharide (LPS) constitutes a vital element of membrane of the gram-negative bacterial cell, triggering vigorous neuroinflammation and facilitating neurodegeneration. Lupeol, a naturally occurring pentacyclic triterpene, has demonstrated several pharmacological properties, notably its anti-inflammatory activity. In this study, we evaluated the anti-inflammatory and anti-Alzheimer activity of lupeol in lipopolysaccharide (LPS)-injected mice model. LPS (250ug/kg) was administered intraperitoneally to C57BL/6 N male mice for 1 week to induce neuroinflammation and cognitive impairment. For biochemical analysis, acetylcholinesterase (AChE) assay, western blotting and confocal microscopy were performed. AChE, western blot and immunofluorescence results showed that lupeol treatment (50 mg/kg) along with LPS administration significantly inhibited the LPS-induced activation of neuroinflammatory mediators and cytokines like nuclear factor (NF-κB), tumor necrosis factor (TNF-α), cyclooxygenase (COX-2) and interleukin (IL-1β). Furthermore, we found that LPS-induced systemic inflammation lead to Alzheimer's symptoms as LPS treatment enhances level of amyloid beta (Aβ), amyloid precursor protein (APP), Beta-site APP cleaving enzyme (BACE-1) and hyperphosphorylated Tau (p-Tau). Lupeol treatment reversed the LPS-induced elevated level of Aβ, APP, BACE-1 and p-Tau in the hippocampus, showing anti-Alzheimer's properties. It is also determined that lupeol prevented LPS-induced synaptic dysfunction via enhanced expression of pre-and post-synaptic markers like SNAP-23, synaptophysin and PSD-95. Overall, our study shows that lupeol prevents memory impairment and synaptic dysfunction via inhibition of neuroinflammatory processes. Hence, we suggest that lupeol might be a useful therapeutic agent in prevention of neuroinflammation-induced neurological disorders like AD., Competing Interests: MOK was employed by the Alz-Dementia Korea Co. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Choe, Park, Park, Tahir, Park and Kim.)