Displaying publications 1 - 20 of 153 in total

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  1. A reappraisal on amyloid cascade hypothesis: the role of chronic infection in Alzheimer's disease
    Phuna ZX, Madhavan P
    Int J Neurosci, 2023 Dec;133(10):1071-1089.
    PMID: 35282779 DOI: 10.1080/00207454.2022.2045290
    Alzheimer disease (AD) is a progressive neurological disorder that accounted for the most common cause of dementia in the elderly population. Lately, 'infection hypothesis' has been proposed where the infection of microbes can lead to the pathogenesis of AD. Among different types of microbes, human immunodeficiency virus-1 (HIV-1), herpes simplex virus-1 (HSV-1), Chlamydia pneumonia, Spirochetes and Candida albicans are frequently detected in the brain of AD patients. Amyloid-beta protein has demonstrated to exhibit antimicrobial properties upon encountering these pathogens. It can bind to microglial cells and astrocytes to activate immune response and neuroinflammation. Nevertheless, HIV-1 and HSV-1 can develop into latency whereas Chlamydia pneumonia, Spirochetes and Candida albicans can cause chronic infections. At this stage, the DNA of microbes remains undetectable yet active. This can act as the prolonged pathogenic stimulus that over-triggers the expression of Aβ-related genes, which subsequently lead to overproduction and deposition of Aβ plaque. This review will highlight the pathogenesis of each of the stated microbial infection, their association in AD pathogenesis as well as the effect of chronic infection in AD progression. Potential therapies for AD by modulating the microbiome have also been suggested. This review will aid in understanding the infectious manifestations of AD.
    Matched MeSH terms: Amyloid; Amyloid beta-Peptides/metabolism
  2. Amyloid precursor protein in Alzheimer's disease
    Maurya R, Bhattacharjee G, Khambhati K, Gohil N, Singh P, Mani I, et al.
    Prog Mol Biol Transl Sci, 2023;196:261-270.
    PMID: 36813361 DOI: 10.1016/bs.pmbts.2022.09.006
    Amyloid precursor protein (APP) is a membrane protein expressed in several tissues. The occurrence of APP is predominant in synapses of nerve cells. It acts as a cell surface receptor and plays a vital role as a regulator of synapse formation, iron export and neural plasticity. It is encoded by the APP gene that is regulated by substrate presentation. APP is a precursor protein activated by proteolytic cleavage and thereby generating amyloid beta (Aβ) peptides which eventually form amyloid plaques that accumulate in Alzheimer's disease patients' brains. In this chapter, we highlight basic mechanism, structure, expression patterns and cleavage of amyloid plaques, and its diagnosis and potential treatment for Alzheimer's disease.
    Matched MeSH terms: Amyloid beta-Peptides/metabolism; Plaque, Amyloid
  3. Cerebrospinal Fluid Amyloid Beta, Tau Levels, Apolipoprotein, and 1H-MRS Brain Metabolites in Alzheimer's Disease: A Systematic Review
    Piersson AD, Mohamad M, Rajab F, Suppiah S
    Acad Radiol, 2021 10;28(10):1447-1463.
    PMID: 32651050 DOI: 10.1016/j.acra.2020.06.006
    BACKGROUND: There is compelling evidence that neurochemical changes measured by proton magnetic resonance spectroscopy (1H-MRS) occur at different phases of Alzheimer's disease (AD). However, the extent to which these neurochemical changes are associated with validated AD biomarkers and/or apolipoprotein (APOE) ε4 is yet to be established.

    OBJECTIVE: This systematic review analyzed the available evidence on (1) neurochemical changes; and (2) the relations between brain metabolite and validated cerebrospinal fluid biomarkers, and/or APOE in AD.

    METHODS: PubMed, Cochrane, Scopus, and gray literature were systematically screened for studies deemed fit for the purpose of the current systematic review.

    RESULTS: Twenty four articles met the inclusion criteria. Decreased levels of N-acetyl aspartate (NAA), NAA/(creatine) Cr, and NAA/(myo-inositol) ml, and increased ml, ml/Cr, Cho (choline)/Cr, and ml/NAA were found in the posterior cingulate cortex/precuneus. Increased ml is associated with increased tau levels, reduced NAA/Cr is associated with increased tau. ml/Cr is negatively correlated with Aβ42, and ml/Cr is positively correlated with t-tau. NAA and glutathione levels are reduced in APOE ε4 carriers. APOE ε4 exerts no modulatory effect on NAA/Cr. There is interaction between APOE ε4, Aβ42, and ml/Cr.

    CONCLUSION: NAA, ml, NAA/Cr, NAA/ml and ml/Cr may be potentially useful biomarkers that may highlight functional changes in the clinical stages of AD. The combinations of ml and tau, NAA/Cr and Aβ42, and NAA/Cr and tau may support the diagnostic process of differentiating MCI/AD from healthy individuals. Large, longitudinal studies are required to clarify the effect of APOE ε4 on brain metabolites.

    Matched MeSH terms: Amyloid beta-Peptides*
  4. Pediococcus pentosaceus LAB6- and Lactiplantibacillus plantarum LAB12-Derived Cell Free Supernatant Inhibited RhoA Activation and Reduced Amyloid-Β In Vitro
    Zaki RM, Ramasamy K, Ahmad Alwi NA, Mohd Yusoff R, Lim SM
    Probiotics Antimicrob Proteins, 2024 Feb;16(1):62-75.
    PMID: 36443559 DOI: 10.1007/s12602-022-10009-7
    Alzheimer's disease (AD) is characterized by aggregation of amyloid beta (Aβ) plaque. RhoA may serve as a potential target for prevention against AD given its role in the amyloidogenic pathway. The recent emergence of the gut-brain axis has linked lactic acid bacteria (LAB) to neuroprotection against AD. This study assessed the importance of RhoA inhibition in mediating the neuroprotective potential of LAB. To this end, de Man, Rogosa and Sharpe (MRS) broth fermented by lactobacilli or pediococci were tested against SK-N-SH (a human neuroblastoma cell line) in the presence of RhoA activator II for 24 h after which the RhoA activity was measured using the G-LISA Kit. Fluorescence staining of f-actin stress fibres was performed to validate RhoA inhibition. SK-N-SH was transfected with plasmid expressing amyloid precursor protein (APP) gene. The Aβ concentration in transfected cells exposed to LAB-derived cell free supernatant (CFS) in the presence of RhoA activator II was measured using the ELISA kit. Furthermore, this study measured organic acids in LAB-derived CFS using the gas chromatography. It was found that LAB-derived CFS yielded strain-dependent inhibition of RhoA, with LAB6- and LAB12-derived CFS being the most potent Pediococcal- and Lactiplantibacillus-based RhoA inhibitor, respectively. Lesser stress fibres were formed under treatment with LAB-derived CFS. The LAB-derived CFS also significantly inhibited Aβ in SK-N-SH transfected with APP gene in the presence of RhoA activator II. The LAB-derived CFS was presented with increased lactic acid, acetic acid, butyric acid and propionic acid. The present findings warrant in-depth study using animal models.
    Matched MeSH terms: Amyloid beta-Peptides/metabolism; Amyloid beta-Protein Precursor/genetics; Amyloid beta-Protein Precursor/metabolism
  5. Aducanumab in Alzheimer's Disease: A Critical Update
    Ashique S, Sirohi E, Kumar S, Rihan M, Mishra N, Bhatt S, et al.
    Curr Med Chem, 2024;31(31):5004-5026.
    PMID: 37497712 DOI: 10.2174/0929867331666230727103553
    Alzheimer's disease (AD) is a complex neurological disorder that results in cognitive decline. The incidence rates of AD have been increasing, particularly among individuals 60 years of age or older. In June 2021, the US FDA approved aducanumab, the first humanized monoclonal antibody, as a potential therapeutic option for AD. Clinical trials have shown this drug to effectively target the accumulation of Aβ (beta-amyloid) plaques in the brain, and its effectiveness is dependent on the dosage and duration of treatment. Additionally, aducanumab has been associated with improvements in cognitive function. Biogen, the pharmaceutical company responsible for developing and marketing aducanumab, has positioned it as a potential breakthrough for treating cerebral damage in AD. However, the drug has raised concerns due to its high cost, limitations, and potential side effects. AD is a progressive neurological condition that affects memory, cognitive function, and behaviour. It significantly impacts the quality of life of patients and caregivers and strains healthcare systems. Ongoing research focuses on developing disease-modifying therapies that can halt or slow down AD progression. The pathogenesis of AD involves various molecular cascades and signaling pathways. However, the formation of extracellular amyloid plaques is considered a critical mechanism driving the development and progression of the disease. Aducanumab, as a monoclonal antibody, has shown promising results in inhibiting amyloid plaque formation, which is the primary pathological feature of AD. This review explores the signaling pathways and molecular mechanisms through which aducanumab effectively prevents disease pathogenesis in AD.
    Matched MeSH terms: Amyloid beta-Peptides/antagonists & inhibitors; Amyloid beta-Peptides/metabolism
  6. Insights into the Pathophysiology of Alzheimer's Disease and Potential Therapeutic Targets: A Current Perspective
    Rajah Kumaran K, Yunusa S, Perimal E, Wahab H, Müller CP, Hassan Z
    J Alzheimers Dis, 2023;91(2):507-530.
    PMID: 36502321 DOI: 10.3233/JAD-220666
    The aging population increases steadily because of a healthy lifestyle and medical advancements in healthcare. However, Alzheimer's disease (AD) is becoming more common and problematic among older adults. AD-related cases show an increasing trend annually, and the younger age population may also be at risk of developing this disorder. AD constitutes a primary form of dementia, an irreversible and progressive brain disorder that steadily damages cognitive functions and the ability to perform daily tasks. Later in life, AD leads to death as a result of the degeneration of specific brain areas. Currently, the cause of AD is poorly understood, and there is no safe and effective therapeutic agent to cure or slow down its progression. The condition is entirely preventable, and no study has yet demonstrated encouraging findings in terms of treatment. Identifying this disease's pathophysiology can help researchers develop safe and efficient therapeutic strategies to treat this ailment. This review outlines and discusses the pathophysiology that resulted in the development of AD including amyloid-β plaques, tau neurofibrillary tangles, neuroinflammation, oxidative stress, cholinergic dysfunction, glutamate excitotoxicity, and changes in neurotrophins level may sound better based on the literature search from Scopus, PubMed, ScienceDirect, and Google Scholar. Potential therapeutic strategies are discussed to provide more insights into AD mechanisms by developing some possible pharmacological agents for its treatment.
    Matched MeSH terms: Amyloid beta-Peptides/metabolism; Plaque, Amyloid/metabolism
  7. An evidence-based review of neuronal cholesterol role in dementia and statins as a pharmacotherapy in reducing risk of dementia
    Dutta S, Rahman S, Ahmad R, Kumar T, Dutta G, Banerjee S, et al.
    Expert Rev Neurother, 2021 12;21(12):1455-1472.
    PMID: 34756134 DOI: 10.1080/14737175.2021.2003705
    INTRODUCTION: Dementia is a progressive neurodegenerative disorder impairing memory and cognition. Alzheimer's Disease, followed by vascular dementia - the most typical form. Risk factors for vascular dementia include diabetes, cardiovascular disease, hyperlipidemia. Lipids' levels are significantly associated with vascular changes in the brain.

    AREAS COVERED: The present article reviews the cholesterol metabolism in the brain, which includes: the synthesis, transport, storage, and elimination process. Additionally, it reviews the role of cholesterol in the pathogenesis of dementia and statin as a therapeutic intervention in dementia. In addition to the above, it further reviews evidence in support of as well as against statin therapy in dementia, recent updates of statin pharmacology, and demerits of use of statin pharmacotherapy.

    EXPERT OPINION: Amyloid-β peptides and intraneuronal neurofibrillary tangles are markers of Alzheimer's disease. Evidence shows cholesterol modulates the functioning of enzymes associated with Amyloid-β peptide processing and synthesis. Lowering cholesterol using statin may help prevent or delay the progression of dementia. This paper reviews the role of statin in dementia and recommends extensive future studies, including genetic research, to obtain a precise medication approach for patients with dementia.

    Matched MeSH terms: Amyloid beta-Peptides/metabolism
  8. The Effects and Mechanisms of Xanthones in Alzheimer's Disease: A Systematic Review
    Pang LW, Hamzah S, Tan SLJ, Mah SH, Yow HY
    Neurochem Res, 2023 Dec;48(12):3485-3511.
    PMID: 37578655 DOI: 10.1007/s11064-023-04005-8
    Xanthones are natural secondary metabolites that possess great potential as neuroprotective agents due to their prominent biological effects on Alzheimer's disease (AD). However, their underlying mechanisms in AD remain unclear. This study aimed to systematically review the effects and mechanisms of xanthones in cell culture and animal studies, gaining a better understanding of their roles in AD. A comprehensive literature search was conducted in the Medline and Scopus databases using specific keywords to identify relevant articles published up to June 2023. After removing duplicates, all articles were imported into the Rayyan software. The article titles were screened based on predefined inclusion and exclusion criteria. Relevant full-text articles were assessed for biases using the OHAT tool. The results were presented in tables. Xanthones have shown various pharmacological effects towards AD from the 21 preclinical studies included. Cell culture studies demonstrated the anti-cholinesterase activity of xanthones, which protects against the loss of acetylcholine. Xanthones exhibited neuroprotective effects by promoting cell viability, reducing the accumulation of β-amyloid and tau aggregation. The administration of xanthones in animal models resulted in a reduction in neuronal inflammation by decreasing microglial and astrocyte burden. In terms of molecular mechanisms, xanthones prevented neuroinflammation through the modulation of signaling pathways, including TLR4/TAK1/NF-κB and MAPK pathways. Mechanisms such as activation of caspase-3 and -9 and suppression of endoplasmic reticulum stress were also reported. Despite the various neuroprotective effects associated with xanthones, there are limited studies reported on their underlying mechanisms in AD. Further studies are warranted to fully understand their potential roles in AD.
    Matched MeSH terms: Amyloid beta-Peptides/metabolism
  9. Enzyme-Mimic Peptide Assembly To Achieve Amidolytic Activity
    Wong YM, Masunaga H, Chuah JA, Sudesh K, Numata K
    Biomacromolecules, 2016 Oct 10;17(10):3375-3385.
    PMID: 27642764
    Amyloid fibers are classified as a new generation of tunable bionanomaterials that exhibit new functions related to their distinctive characteristics, such as their universality, tunability, and stiffness. Here, we introduce the catalytic residues of serine protease into a peptide catalyst (PC) via an enzyme-mimic approach. The rational design of a repeating pattern of polar and nonpolar amino acids favors the conversion of the peptides into amyloid-like fibrils via self-assembly. Distinct fibrous morphologies have been observed at different pH values and temperatures, which indicates that different fibril packing schemes can be designed; hence, fibrillar peptides can be used to generate efficient artificial catalysts for amidolytic activities at mild pH values. The results of atomic force microscopy, Raman spectroscopy, and wide-angle X-ray scattering analyses are used to discuss and compare the fibril structure of a fibrillar PC with its amidolytic activity. The pH of the fibrillation reaction crucially affects the pKa of the side chains of the catalytic triads and is important for stable fibril formation. Temperature is another important parameter that controls the self-assembly of peptides into highly stacked and laminated morphologies. The morphology and stability of fibrils are crucial and represent important factors for demonstrating the capability of the peptides to exert amidolytic activity. The observed amidolytic activity of PC4, one of the PCs, was validated using an inhibition assay, which revealed that PC4 can perform enzyme-like amidolytic catalysis. These results provide insights into the potential use of designed peptides in the generation of efficient artificial enzymes.
    Matched MeSH terms: Amyloid/ultrastructure; Amyloid/chemistry*; Amyloid beta-Peptides/ultrastructure; Amyloid beta-Peptides/chemistry*
  10. Fulltext Fibrillary deposits: amyloids and tactoids
    Looi LM
    Malays J Pathol, 1995 Jun;17(1):1-10.
    PMID: 8906998
    Two forms of abnormal fibrillary protein deposition are considered: amyloidosis and fibrillary (immunotactoid) glomerulonephritis. Amyloid is characterised by an antiparallel, beta-pleated configuration which imparts to it a unique apple-green birefringence after Congo red staining. Inspite of its fairly constant physical properties, the chemical composition of amyloid fibrils is amazingly diverse, encomposing AA protein, light chain fragments, transthyretin, procalcitonin, islet amyloid polypeptide, atrial natriuretic peptides, beta-amyloid protein, beta-2-microglobulin, cystatin C, gelsolin, apolipoprotein A1, lyzozyme and their mutant variants. Amyloid P component and heparan sulphate proteoglycan are ubiquitous non-fibrillary amyloid components which have significant roles in the amyloidogenetic process, as do also precursor fibril proteins. Different amyloid fibril proteins relate to different amyloidosis syndromes and different histological patterns, and provide the basis for new diagnostic approaches to this disorder. Glomerular deposits in fibrillary glomerulonephritis (FGN), although often mistaken for amyloid, differ from it in its negative Congophilia, wider fibril width and highly organised, microtubular-tactoidal appearance ultrastructurally. FGN is essentially a primary glomerulopathy resulting in progressive renal failure. Despite certain differences, intriguing similarities between both entities of fibrillary deposition pose a challenge to researchers as to the mechanisms of abnormal protein crystallization and fibril formation in tissues.
    Matched MeSH terms: Amyloid/ultrastructure; Amyloid/chemistry; Serum Amyloid A Protein/chemistry; Amyloidosis/etiology; Amyloidosis/pathology*; Amyloid beta-Peptides/chemistry
  11. Mechanisms of action of amyloid-beta and its precursor protein in neuronal cell death
    Leong YQ, Ng KY, Chye SM, Ling APK, Koh RY
    Metab Brain Dis, 2020 01;35(1):11-30.
    PMID: 31811496 DOI: 10.1007/s11011-019-00516-y
    Extracellular senile plaques and intracellular neurofibrillary tangles are the neuropathological findings of the Alzheimer's disease (AD). Based on the amyloid cascade hypothesis, the main component of senile plaques, the amyloid-beta (Aβ) peptide, and its derivative called amyloid precursor protein (APP) both have been found to place their central roles in AD development for years. However, the recent therapeutics have yet to reverse or halt this disease. Previous evidence demonstrates that the accumulation of Aβ peptides and APP can exert neurotoxicity and ultimately neuronal cell death. Hence, we discuss the mechanisms of excessive production of Aβ peptides and APP serving as pathophysiologic stimuli for the initiation of various cell signalling pathways including apoptosis, necrosis, necroptosis and autophagy which lead to neuronal cell death. Conversely, the activation of such pathways could also result in the abnormal generation of APP and Aβ peptides. An elucidation of actions of APP and its metabolite, Aβ, could be vital in suggesting novel therapeutic opportunities.
    Matched MeSH terms: Amyloid beta-Peptides/genetics; Amyloid beta-Peptides/metabolism*; Amyloid beta-Protein Precursor/genetics; Amyloid beta-Protein Precursor/metabolism*
  12. Fulltext Fluorine-19 Magnetic Resonance Imaging for Detection of Amyloid β Oligomers Using a Keto Form of Curcumin Derivative in a Mouse Model of Alzheimer's Disease
    Yanagisawa D, Ibrahim NF, Taguchi H, Morikawa S, Tomiyama T, Tooyama I
    Molecules, 2021 Mar 04;26(5).
    PMID: 33806326 DOI: 10.3390/molecules26051362
    Recent evidence suggests that the formation of soluble amyloid β (Aβ) aggregates with high toxicity, such as oligomers and protofibrils, is a key event that causes Alzheimer's disease (AD). However, understanding the pathophysiological role of such soluble Aβ aggregates in the brain in vivo could be difficult due to the lack of a clinically available method to detect, visualize, and quantify soluble Aβ aggregates in the brain. We had synthesized a novel fluorinated curcumin derivative with a fixed keto form, named as Shiga-Y51, which exhibited high selectivity to Aβ oligomers in vitro. In this study, we investigated the in vivo detection of Aβ oligomers by fluorine-19 (19F) magnetic resonance imaging (MRI) using Shiga-Y51 in an APP/PS1 double transgenic mouse model of AD. Significantly high levels of 19F signals were detected in the upper forebrain region of APP/PS1 mice compared with wild-type mice. Moreover, the highest levels of Aβ oligomers were detected in the upper forebrain region of APP/PS1 mice in enzyme-linked immunosorbent assay. These findings suggested that 19F-MRI using Shiga-Y51 detected Aβ oligomers in the in vivo brain. Therefore, 19F-MRI using Shiga-Y51 with a 7 T MR scanner could be a powerful tool for imaging Aβ oligomers in the brain.
    Matched MeSH terms: Amyloid beta-Peptides/metabolism*; Amyloid beta-Peptides/chemistry; Plaque, Amyloid/metabolism; Plaque, Amyloid/pathology*
  13. Fulltext The pattern of amyloid deposition in the lung
    Looi LM
    Malays J Pathol, 1999 Jun;21(1):29-35.
    PMID: 10879276
    A review of routine histopathological samples and autopsies examined at the Department of Pathology, University of Malaya revealed 15 cases of amyloidosis of the lung. Two were localized depositions limited to the lung while in the remainder, lung involvement was part of the picture of systemic amyloidosis. Both cases of localized amyloidosis presented with symptomatic lung/bronchial masses and a clinical diagnosis of tumour. Histology revealed "amyloidomas" associated with heavy plasma cell and lymphocytic infiltration and the presence of multinucleated giant cells. In both cases, the amyloid deposits were immunopositive for lambda light chains and negative for kappa chains and AA protein. One was a known systemic lupus erythematosus patient with polyclonal hypergammaglobulinaemia. The other patient was found to have plasma cell dyscrasia with monoclonal IgG lambda gammopathy. Both patients did not develop systemic amyloidosis. In contrast, lung involvement in systemic AA amyloidosis was not obvious clinically or macroscopically but was histologically evident in 75% of cases subjected to autopsy. Amyloid was detected mainly in the walls of arterioles and small vessels, and along the alveolar septa. It was less frequently detected in the pleura, along the basement membrane of the bronchial epithelium and around bronchial glands. In one case of systemic AL amyloidosis associated with multiple myeloma, an "amyloidoma" occurred in the subpleural region reminiscent of localized amyloidosis. These cases pose questions on (1) whether localized "tumour-like" amyloidosis is a forme fruste of systemic AL amyloidosis and (2) the differing pattern of tissue deposition of different chemical types of amyloid fibrils, with the suggestion that light chain amyloid has a greater tendency to nodular deposition than AA amyloid.
    Matched MeSH terms: Amyloid/metabolism*; Amyloidosis/metabolism*
  14. Transcorneal electrical stimulation enhances cognitive functions in aged and 5XFAD mouse models
    Yu WS, Aquili L, Wong KH, Lo ACY, Chan LLH, Chan YS, et al.
    Ann N Y Acad Sci, 2022 09;1515(1):249-265.
    PMID: 35751874 DOI: 10.1111/nyas.14850
    Dementia is a major burden on global health for which there are no effective treatments. The use of noninvasive visual stimulation to ameliorate cognitive deficits is a novel concept that may be applicable for treating dementia. In this study, we investigated the effects of transcorneal electrical stimulation (TES) on memory enhancement using two mouse models, in aged mice and in the 5XFAD model of Alzheimer's disease. After 3 weeks of TES treatment, mice were subjected to Y-maze and Morris water maze tests to assess hippocampal-dependent learning and memory. Immunostaining of the hippocampus of 5XFAD mice was also performed to examine the effects of TES on amyloid plaque pathology. The results showed that TES improved the performance of both aged and 5XFAD mice in memory tests. TES also reduced hippocampal plaque deposition in male, but not female, 5XFAD mice. Moreover, TES significantly reversed the downregulated level of postsynaptic protein 95 in the hippocampus of male 5XFAD mice, suggesting the effects of TES involve a postsynaptic mechanism. Overall, these findings support further investigation of TES as a potential treatment for cognitive dysfunction and mechanistic studies of TES effects in other dementia models.
    Matched MeSH terms: Plaque, Amyloid/pathology
  15. Fulltext Phytochemical Compounds and Nanoparticles as Phytochemical Delivery Systems for Alzheimer's Disease Management
    Bakrim S, Aboulaghras S, El Menyiy N, El Omari N, Assaggaf H, Lee LH, et al.
    Molecules, 2022 Dec 19;27(24).
    PMID: 36558176 DOI: 10.3390/molecules27249043
    Alzheimer's disease remains one of the most widespread neurodegenerative reasons for dementia worldwide and is associated with considerable mortality and morbidity. Therefore, it has been considered a priority for research. Indeed, several risk factors are involved in the complexity of the therapeutic ways of this pathology, including age, traumatic brain injury, genetics, exposure to aluminum, infections, diabetes, vascular diseases, hypertension, dyslipidemia, and obesity. The pathophysiology of Alzheimer's disease is mostly associated with hyperphosphorylated protein in the neuronal cytoplasm and extracellular plaques of the insoluble β-amyloid peptide. Therefore, the management of this pathology needs the screening of drugs targeting different pathological levels, such as acetylcholinesterase (AchE), amyloid β formation, and lipoxygenase inhibitors. Among the pharmacological strategies used for the management of Alzheimer's disease, natural drugs are considered a promising therapeutic strategy. Indeed, bioactive compounds isolated from different natural sources exhibit important anti-Alzheimer effects by their effectiveness in promoting neuroplasticity and protecting against neurodegeneration as well as neuroinflammation and oxidative stress in the brain. These effects involve different sub-cellular, cellular, and/or molecular mechanisms, such as the inhibition of acetylcholinesterase (AchE), the modulation of signaling pathways, and the inhibition of oxidative stress. Moreover, some nanoparticles were recently used as phytochemical delivery systems to improve the effects of phytochemical compounds against Alzheimer's disease. Therefore, the present work aims to provide a comprehensive overview of the key advances concerning nano-drug delivery applications of phytochemicals for Alzheimer's disease management.
    Matched MeSH terms: Amyloid beta-Peptides/metabolism
  16. Fulltext Lysosomal dysfunction induced cytosolic vacuolation and increased intracellular amyloid-beta 42 (Aβ42) in human brain endothelial cells (HBEC-5i)
    Laili IN, Nasir MHM, Jufri NF, Ibrahim FW, Hamid A
    Biomed Pharmacother, 2023 May;161:114501.
    PMID: 36931027 DOI: 10.1016/j.biopha.2023.114501
    Lysosome is a primary degradative organelle and is crucial in cellular homeostasis. A reduction in its function due to ageing has been associated with the development of Alzheimer's disease (AD), a common neurodegenerative disorder characterised by the deposition of neurotoxic amyloid plaque in the brain and cerebral vessel walls. The breakdown of the blood-brain barrier (BBB) plays a vital role in the pathogenesis of AD. However, the impact of lysosomal dysfunction on brain endothelial cells, the key component of the BBB, in the disease progression is yet to be fully understood. In this study, human brain endothelial cells (HBEC-5i) were exposed to a lysosomotropic compound, chloroquine (CQ) for 24 h. Cell viability was assessed with the 3-(4,5-dimethylthiazol-2-yl)- 2,5-diphenyltetrazolium bromide (MTT) assay to determine the inhibitory concentration (IC) at IC10 (17.5 µM), IC25 (70.5 µM), and IC50 (125 µM). The morphological changes observed include vacuoles arrested in the cytosols and cell shrinkage that were more prominent at IC25 and IC50. Lysosomal dysfunction was evaluated by measuring the lysosomal-associated membrane protein-1 (LAMP-1) and microtubule-associated protein light chain 3-II (LC3-II) using the capillary-based immunoassay. LC3-II was significantly increased at IC25 and IC50 (p 
    Matched MeSH terms: Amyloid beta-Peptides/metabolism
  17. Environmental enrichment improves cognitive function, learning, memory and anxiety-related behaviours in rodent models of dementia: Implications for future study
    Mohd Sahini SN, Mohd Nor Hazalin NA, Srikumar BN, Jayasingh Chellammal HS, Surindar Singh GK
    Neurobiol Learn Mem, 2024 Feb;208:107880.
    PMID: 38103676 DOI: 10.1016/j.nlm.2023.107880
    Environmental enrichment (EE) is a process of brain stimulation by modifying the surroundings, for example, by changing the sensory, social, or physical conditions. Rodents have been used in such experimental strategies through exposure to diverse physical, social, and exploration conditions. The present study conducted an extensive analysis of the existing literature surrounding the impact of EE on dementia rodent models. The review emphasised the two principal aspects that are very closely related to dementia: cognitive function (learning and memory) as well as psychological factors (anxiety-related behaviours such as phobias and unrealistic worries). Also highlighted were the mechanisms involved in the rodent models of dementia showing EE effects. Two search engines, PubMed and Science Direct, were used for data collection using the following keywords: environmental enrichment, dementia, rodent model, cognitive performance, and anxiety-related behaviour. Fifty-five articles were chosen depending on the criteria for inclusion and exclusion. The rodent models with dementia demonstrated improved learning and memory in the form of hampered inflammatory responses, enhanced neuronal plasticity, and sustained neuronal activity. EE housing also prevented memory impairment through the prevention of amyloid beta (Aβ) seeding formation, an early stage of Aβ plaque formation. The rodents subjected to EE were observed to present increased exploratory activity and exert less anxiety-related behaviour, compared to those in standard housing. However, some studies have proposed that EE intervention through exercise would be too mild to counteract the anxiety-related behaviour and risk assessment behaviour deficits in the Alzheimer's disease rodent model. Future studies should be conducted on old-aged rodents and the duration of EE exposure that would elicit the greatest benefits since the existing studies have been conducted on a range of ages and EE durations. In summary, EE had a considerable effect on dementia rodent models, with the most evident being improved cognitive function.
    Matched MeSH terms: Amyloid beta-Peptides*
  18. Fulltext Linking Diabetes to Alzheimer's Disease: Potential Roles of Glucose Metabolism and Alpha-Glucosidase
    Wee AS, Nhu TD, Khaw KY, Tang KS, Yeong KY
    Curr Neuropharmacol, 2023;21(10):2036-2048.
    PMID: 36372924 DOI: 10.2174/1570159X21999221111102343
    Alzheimer's disease (AD) and type 2 diabetes mellitus (DM) are more prevalent with ageing and cause a substantial global socio-economic burden. The biology of these two conditions is well elaborated, but whether AD and type 2 DM arise from coincidental roots in ageing or are linked by pathophysiological mechanisms remains unclear. Research findings involving animal models have identified mechanisms shared by both AD and type 2 DM. Deposition of β-amyloid peptides and formation of intracellular neurofibrillary tangles are pathological hallmarks of AD. Type 2 DM, on the other hand, is a metabolic disorder characterised by hyperglycaemia and insulin resistance. Several studies show that improving type 2 DM can delay or prevent the development of AD, and hence, prevention and control of type 2 DM may reduce the risk of AD later in life. Alpha-glucosidase is an enzyme that is commonly associated with hyperglycaemia in type 2 DM. However, it is uncertain if this enzyme may play a role in the progression of AD. This review explores the experimental evidence that depicts the relationship between dysregulation of glucose metabolism and AD. We also delineate the links between alpha-glucosidase and AD and the potential role of alpha-glucosidase inhibitors in treating AD.
    Matched MeSH terms: Amyloid beta-Peptides/metabolism
  19. Ala97Ser mutation is common among ethnic Chinese Malaysians with transthyretin familial amyloid polyneuropathy
    Low SC, Tan CY, Md Sari NA, Ahmad-Annuar A, Wong KT, Lin KP, et al.
    Amyloid, 2019 7 26;26(sup1):7-8.
    PMID: 31343308 DOI: 10.1080/13506129.2019.1582479
    Matched MeSH terms: Amyloid Neuropathies, Familial/genetics*; Amyloid Neuropathies, Familial/epidemiology; Amyloid Neuropathies, Familial/pathology
  20. Evaluation of the Expression of Amyloid Precursor Protein and the Ratio of Secreted Amyloid Beta 42 to Amyloid Beta 40 in SH-SY5Y Cells Stably Transfected with Wild-Type, Single-Mutant and Double-Mutant Forms of the APP Gene for the Study of Alzheimer's Disease Pathology
    Pahrudin Arrozi A, Shukri SNS, Wan Ngah WZ, Mohd Yusof YA, Ahmad Damanhuri MH, Makpol S
    Appl Biochem Biotechnol, 2017 Nov;183(3):853-866.
    PMID: 28417423 DOI: 10.1007/s12010-017-2468-6
    Neuroblastoma cell lines such as SH-SY5Y are the most frequently utilized models in neurodegenerative research, and their use has advanced the understanding of the pathology of neurodegeneration over the past few decades. In Alzheimer's disease (AD), several pathogenic mutations have been described, all of which cause elevated levels of pathological hallmarks such as amyloid-beta (Aβ). Although the genetics of Alzheimer's disease is well known, familial AD only accounts for a small number of cases in the population, with the rest being sporadic AD, which contains no known mutations. Currently, most of the in vitro models used to study AD pathogenesis only examine the level of Aβ42 as a confirmation of successful model generation and only perform comparisons between wild-type APP and single mutants of the APP gene. Recent findings have shown that the Aβ42/40 ratio in cerebrospinal fluid (CSF) is a better diagnostic indicator for AD patients than is Aβ42 alone and that more extensive Aβ formation, such as accumulation of intraneuronal Aβ, Aβ plaques, soluble oligomeric Aβ (oAβ), and insoluble fibrillar Aβ (fAβ) occurs in TgCRND8 mice expressing a double-mutant form (Swedish and Indiana) of APP, later leading to greater progressive impairment of the brain. In this study, we generated SH-SY5Y cells stably transfected separately with wild-type APP, the Swedish mutation of APP, and the Swedish and Indiana mutations of APP and evaluated the APP expression as well as the Aβ42/40 ratio in those cells. The double-mutant form of APP (Swedish/Indiana) expressed markedly high levels of APP protein and showed a high Aβ2/40 ratio compared to wild-type and single-mutant cells.
    Matched MeSH terms: Amyloid beta-Peptides/secretion*; Amyloid beta-Protein Precursor/genetics*
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