Recent Advances in Therapeutics for the Treatment of Alzheimer’s Disease

Molecules, Journal Year: 2024, Volume and Issue: 29(21), P. 5131 - 5131

Published: Oct. 30, 2024

The most prevalent chronic neurodegenerative illness in the world is Alzheimer's disease (AD). It results mental symptoms including behavioral abnormalities and cognitive impairment, which have a substantial financial psychological impact on relatives of patients. review discusses various pathophysiological mechanisms contributing to AD, amyloid beta, tau protein, inflammation, other factors, while emphasizing need for effective disease-modifying therapeutics that alter progression rather than merely alleviating symptoms. This mainly covers medications are now being studied clinical trials or recently approved by FDA fall under treatment (DMT) category, alters targeting underlying biological DMTs focus improving patient outcomes slowing decline, enhancing neuroprotection, supporting neurogenesis. Additionally, amyloid-targeting therapies, tau-targeting neuroprotective others. evaluation specifically looked at studies FDA-approved novel Phase II III development were carried out between 2021 2024. A thorough US government database identified biologics small molecule drugs 14 agents I, 34 II, 11 might be completed 2028.

Language: Английский

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Two- and Three-Dimensional In Vitro Models of Parkinson’s and Alzheimer’s Diseases: State-of-the-Art and Applications

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(2), P. 620 - 620

Published: Jan. 13, 2025

In vitro models play a pivotal role in advancing our understanding of neurodegenerative diseases (NDs) such as Parkinson’s and Alzheimer’s disease (PD AD). Traditionally, 2D cell cultures have been instrumental elucidating the cellular mechanisms underlying these diseases. Cultured cells derived from patients or animal provide valuable insights into pathological processes at level. However, they often lack native tissue environment complexity, limiting their ability to fully recapitulate features. contrast, 3D offer more physiologically relevant platform by mimicking brain architecture. These can incorporate multiple types, including neurons, astrocytes, microglia, creating microenvironment that closely resembles brain’s complexity. Bioengineering approaches allow researchers better replicate cell–cell interactions, neuronal connectivity, disease-related phenotypes. Both advantages limitations. While simplicity scalability for high-throughput screening basic processes, enhanced physiological relevance Integrating findings both model systems NDs, ultimately aiding development novel therapeutic strategies. Here, we review existing study PD AD.

Language: Английский

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Investigation of the Acute Effects of Two Different Preoxygenation Methods on Neurodegenerative Biomarkers in Laparoscopic Cholecystectomy Surgery

Medicina, Journal Year: 2025, Volume and Issue: 61(2), P. 167 - 167

Published: Jan. 21, 2025

Background and Objectives: Oxygen is essential for all living organisms plays a critical role in anesthesia intensive care practices. However, the notion that unlimited oxygen therapy harmless misconception. Our study investigates acute effects of different preoxygenation methods on hemodynamic parameters neurodegenerative biomarkers patients undergoing laparoscopic cholecystectomy surgery. Materials Methods: This prospective, randomized, controlled included 52 elective under general anesthesia. Patients were divided into two groups: Group I received standard (100% FiO2 3 min), while II underwent rapid (eight deep breaths over 30 s to 1 min). Hemodynamic (SAP, DAP, MAP, SpO2) (pTau, S100B, NSE, NfL, GFAP) measured after preoxygenation, intubation, at end Results: exhibited significant increase levels pTau, GFAP, indicating higher neuronal glial cell stress compared (p < 0.001). No NfL was observed either group. (HR, SAP, MAP) significantly during I, suggesting an increased response. showed lower neurotoxicity oxidative stress. Conclusions: findings indicate with 100% induces cells, axons, leading biomarkers. Optimizing strategies crucial reduce improve neurological outcomes surgical patients.

Language: Английский

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Exploring Alzheimer's Disease Treatment: Established Therapies and Novel Strategies for Future Care

European Journal of Pharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 177520 - 177520

Published: March 1, 2025

Language: Английский

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A Focus on the Link Between Metal Dyshomeostasis, Norepinephrine, and Protein Aggregation

Antioxidants, Journal Year: 2025, Volume and Issue: 14(3), P. 347 - 347

Published: March 15, 2025

Neurodegenerative disorders are one of the main public health problems worldwide and, for this reason, they have attracted attention several researchers who aim to better understand molecular processes linked etiology these disorders, including Alzheimer's and Parkinson's diseases. In review, we describe both beneficial toxic effect norepinephrine (NE) its connected ROS/metal-mediated pathways, which end in neuromelanin (NM) formation protein aggregation. particular, emphasize importance stabilizing delicate homeostatic balance that regulates (i) metal/ROS-promoted oxidation catecholamines, as NE, (ii) generation oxidative by-products capable covalently non-covalently modifying neuroproteins, thus altering their stability oligomerization; may (iii) incorporation conjugates into vesicles, then evolve organelles. general, provide an up-to-date overview challenges controversies emerging from current literature delineate a direction future research.

Language: Английский

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The Molecular Mechanism of miRNA‐195‐5p Regulating ERK Involvement in Abnormal Phosphorylation of Tau Protein by Aluminum Maltol in PC12 Cells

Journal of Applied Toxicology, Journal Year: 2025, Volume and Issue: unknown

Published: April 24, 2025

ABSTRACT Although aluminum is ubiquitously present on Earth, it not necessary for life. Aluminum a metal element that can induce neurotoxicity. The neurotoxicity of mainly caused by the aggregation abnormally phosphorylated tau protein to form neurofibrillary tangles (NFTs). phosphorylation regulated both kinases and phosphatases. ERK involved in PHF‐type hyperphosphorylation. Recent studies have revealed interaction between microRNAs (miRNAs) ERK/MAPK cascade related maintaining normal function nervous system. miR‐195 early development AD with potential impact cognition. Therefore, we speculate miRNA‐195 may regulate activity, thereby causing hyperphosphorylation purpose this study was explore role miRNA‐195‐5p regulating process maltol‐induced results showed exposure decreased expression level increased P‐ERK, abnormal tau. After inhibiting activity ERK, decreased. There an effect proteins. overexpression miRNA‐195‐5p, inhibited. In conclusion, regulates involvement Al (mal)3in PC12 cells.

Language: Английский

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Neuroprotective Assessment of Nutraceutical (Betanin) in Neuroblastoma Cell Line SHSY-5Y: An in-Vitro and in-Silico Approach

Neurochemical Research, Journal Year: 2024, Volume and Issue: 50(1)

Published: Dec. 11, 2024

Language: Английский

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Unlocking Therapeutic Potential of siRNA-based Drug Delivery System for Treatment of Alzheimer's Disease

Journal of Drug Delivery Science and Technology, Journal Year: 2024, Volume and Issue: unknown, P. 106413 - 106413

Published: Nov. 1, 2024

Language: Английский

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Inhibition of Protease Activated Receptor-2 Activation in Parkinson’s Disease

Published: July 4, 2024

In Parkinson's disease, neuroinflammation is a complex defense mechanism. Activated microglia and Proteinase-activated receptor-2 (PAR2) are key points in the regulation of neuroinflammation. 1-Piperidin Propionic Acid (1-PPA) has been recently described as novel inhibitor PAR2. The aim our study was to evaluate effect 1-PPA microglial activation disease. Protein aggregates PAR2 expression were analyzed by thioflavin S assay immunofluorescence cultured human fibroblasts from patients, treated or not with 1-PPA. A significant decrease amyloid observed after treatment all patients. parallel expression, that higher sporadic Parkinson&rsquo;s also both at transcriptional protein level. addition, mouse LPS-activated microglia, inflammatory profile significantly downregulated treatment, remarkable IL-1, IL-6 TNF-togheter decreased expression.In conclusion, determines reduced neuroglia inflammation formation, suggesting pharmacological inhibition could be proposed strategy control

Language: Английский

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Aging device: tau protein transposes the telomere fragment into promoter/enhancer to promote gene copy number decrement regulation

Published: Aug. 2, 2024

The reasons for the significant impact of abnormal tau protein phosphorylation and aggregation on Alzheimer's disease are still unknown. This study used bioinformatics methods, including domain search tools, to investigate pathogenic mechanism in neurodegenerative diseases. reveals that possesses domains linked Aging Device. These include pyruvate kinase, phosphatase, telomere binding, transposition, HNH cas9, replicon helicase, DNA polymerase, nuclease, transcription factors-like, promoter binding (TATA-box), enhancer (Homeobox, MADS-box, HMG box), mitochondrial localization mtDNA polymerase. It implies protein's kinase supplies ATP energy its Device function. Cas9 , reverse transcriptase, transposase cut sequence between "TAA" from then transcript guide RNA sequence. factor slides specific region. excises intron region complementary RAN nuclease splice or add fragment We thought transposes fragments promoter/enhancer might mess up polymerase II, which would help Device's telomere-guided gene (DNA nucleus mitochondrial) copy number decrement regulation system work better. can us understand how stress injuries, like low blood sugar oxygen levels, cause clump together phosphorylate, turns off a way doesn't make sense. Thus, anomalous aging devices, such as protein, may be associated with diseases Alzheimer disease, amyotrophic lateral sclerosis.

Language: Английский

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