Alzheimer's Disease Investigated via Gene-Environment Interactions, Biochemical Pathways, Cellular Processes, and Disease Phenotype Variability DOI Creative Commons
Viqas Shafi,

Ifrah Siddiqui

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: May 14, 2024

Abstract Background: Alzheimer's disease (AD) is a neurodegenerative disorder influenced by genetic and environmental factors. APOE, APP, PSEN1, PSEN2, CLU, SORL1, BIN1, CR1, PICALM, TREM2, ABCA7, CD33 play key roles in AD pathogenesis, affecting biochemical pathways cellular processes. However, the interaction between predisposition factors, as well reasons for variability phenotype, remain poorly understood. This study aims to investigate these interactions improve our understanding of etiology inform personalized interventions. Methods: A comprehensive search encompassing databases such PubMed, MEDLINE, Google Scholar, open access/subscription-based journals was conducted retrieve relevant articles investigation genes involved including CD33. Articles were searched without any date restrictions. Utilizing criteria delineated methodology section, studies systematically reviewed elucidate how factors genetics influence onset, progression, symptom severity, progression rates. adheres PRISMA guidelines (Preferred Reporting Items Systematic Reviews Meta-Analyses). Results: Our revealed complicated predisposition, pathways, processes pathogenesis. amyloid-beta production, tau pathology, lipid metabolism, inflammation AD. These interact with diet, pollutants, head trauma, lifestyle, modulating risk progression. Additionally, we found phenotype among individuals carrying similar mutations, modifiers, cognitive reserve, neurobiological differences. Conclusion: multifactorial critical pathogenesis inflammation. further Understanding essential developing interventions delay reduce slow

Language: Английский

Microglial activation states and their implications for Alzheimer's Disease DOI Creative Commons

Zachary Valiukas,

Kathy Tangalakis, Vasso Apostolopoulos

et al.

The Journal of Prevention of Alzheimer s Disease, Journal Year: 2025, Volume and Issue: 12(1), P. 100013 - 100013

Published: Jan. 1, 2025

Alzheimer's Disease (AD) is a chronic neurodegenerative disorder characterized by the accumulation of toxic amyloid-beta (Aβ) plaques and neurofibrillary tangles (NFTs) tau protein in brain. Microglia, key immune cells central nervous system, play an important role AD development progression, primarily through their responses to Aβ NFTs. Initially, microglia can clear Aβ, but AD, activation overwhelms protective mechanisms, leading sustained neuroinflammation that enhances plaque toxicity, setting off damaging cycle affects neurons, astrocytes, cerebral vasculature, other microglia. Current treatments have been largely ineffective, though emerging immunotherapies focusing on removal show promise, often overlook neuroinflammation. Activated display complex range phenotypes be broadly broken into pro- or anti-inflammatory states, although this dichotomy does not describe significant overlap between states. strongly induce inflammatory activity, triggering production reactive oxygen species, cytokines (e.g., TNF-α, IL-1β, IL-6), synapse engulfment, blood-brain barrier compromise, impaired clearance. These processes contribute neural tissue loss, manifesting as cognitive decline such executive function memory. Conversely, exerts neuroprotective effects suppressing pathways releasing neurotrophic factors aid neuron repair protection. Induction states may offer dual therapeutic approach address both AD. This suggests potential strategies modulate microglial phenotypes, aiming restore functions mitigate disease progression simultaneously targeting inflammation pathology.

Language: Английский

Citations

4
Classifying Beta-Secretase 1 Inhibitor Activity for Alzheimer’s Drug Discovery with LightGBM DOI Creative Commons
Teuku Rizky Noviandy, Khairun Nisa, Ghalieb Mutig Idroes

et al.

Journal of Computing Theories and Applications, Journal Year: 2024, Volume and Issue: 1(4), P. 358 - 367

Published: March 10, 2024

This study explores the utilization of LightGBM, a gradient-boosting framework, to classify inhibitory activity beta-secretase 1 inhibitors, addressing challenges Alzheimer's disease drug discovery. The aims enhance classification performance by focusing on overcoming limitations traditional statistical models and conventional machine-learning techniques in handling complex molecular datasets. By sourcing dataset 7298 compounds from ChEMBL database calculating descriptors for each compound as features, we employed LightGBM conjunction with set carefully selected achieve nuanced analysis activities. model's efficiency was benchmarked against algorithms, revealing LightGBM's superior accuracy (84.93%), precision (87.14%), sensitivity (89.93%), specificity (77.63%), F1-score (88.17%) classifying inhibitor activity. underscores critical role understanding efficacy, highlighting potential streamlining virtual screening process. Conclusively, findings advocate adoption computational discovery, offering promising avenue advancing therapeutic development facilitating identification candidates enhanced reliability.

Language: Английский

Citations

14
Neurodegenerative Disease: From Molecular Basis to Therapy DOI Open Access
Claudia Ricci

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(2), P. 967 - 967

Published: Jan. 12, 2024

Neurodegenerative diseases are a heterogeneous group of age-related disorders characterised by the progressive degeneration or death neurons in central peripheral nervous system [...].

Language: Английский

Citations

11
The Role of Sirtuin 1 in Ageing and Neurodegenerative Disease: A Molecular Perspective DOI
Riya Thapa, Ehssan Moglad, Muhammad Afzal

et al.

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 102, P. 102545 - 102545

Published: Oct. 17, 2024

Language: Английский

Citations

10
Quercetin ameliorates neuroinflammatory and neurodegenerative biomarkers in the brain and improves neurobehavioral parameters in a repeated intranasal amyloid-beta exposed model of Alzheimer's disease DOI
Vaibhav Lasure, Avtar Singh Gautam, Rakesh Kumar Singh

et al.

Food & Function, Journal Year: 2024, Volume and Issue: 15(17), P. 8712 - 8728

Published: Jan. 1, 2024

Quercetin exerted antioxidant and anti-inflammatory properties to protect brain neuronal health. It also ameliorated Aβ deposition, regulated APP, BACE-1 tau hyperphosphorylation in brain, improved neurobehavioral cognitive parameters.

Language: Английский

Citations

8
Impact of GSK-3β and CK-1δ on Wnt signaling pathway in alzheimer disease: A dual target approach DOI
Vinita Sharma, Prabodh Chander Sharma,

Jurnal Reang

et al.

Bioorganic Chemistry, Journal Year: 2024, Volume and Issue: 147, P. 107378 - 107378

Published: April 17, 2024

Language: Английский

Citations

5
Mechanisms of mitophagy and oxidative stress in cerebral ischemia–reperfusion, vascular dementia, and Alzheimer’s disease DOI Creative Commons

Yu-Jie Lyu,

Zhipeng Meng,

Yun‐Yun Hu

et al.

Frontiers in Molecular Neuroscience, Journal Year: 2024, Volume and Issue: 17

Published: Aug. 7, 2024

Neurological diseases have consistently represented a significant challenge in both clinical treatment and scientific research. As research has progressed, the significance of mitochondria pathogenesis progression neurological become increasingly prominent. Mitochondria serve not only as source energy, but also regulators cellular growth death. Both oxidative stress mitophagy are intimately associated with mitochondria, there is mounting evidence that exert pivotal regulatory influence on diseases. In recent years, been notable rise prevalence cerebral ischemia/reperfusion injury (CI/RI), vascular dementia (VaD), Alzheimer’s disease (AD), which collectively represent public health concern. Reduced levels observed CI/RI, VaD AD. The improvement pathology demonstrated through increase levels. CI/RI results tissue ischemia hypoxia, causes stress, disruption blood–brain barrier (BBB) damage to vasculature. BBB may induce or exacerbate some extent. addition, inadequate perfusion due altered function accumulation amyloid β (Aβ) thereby contributing exacerbating AD pathology. Intravenous plasminogen activator (tPA; alteplase) endovascular thrombectomy effective treatments for stroke. However, narrow window opportunity administration tPA thrombectomy, markedly elevated incidence disability among patients CI/RI. It regrettable currently no still specific drugs Despite availability U.S. Food Drug Administration (FDA)-approved first-line AD, including memantine, donepezil hydrochloride, galantamine, these agents do fundamentally block pathological process this paper, we undertake review mechanisms disorders, summary trials conducted proposal new strategy targeted disorders based stress.

Language: Английский

Citations

5
Decoding Neurodegeneration: A Review of Molecular Mechanisms and Therapeutic Advances in Alzheimer’s, Parkinson’s, and ALS DOI Open Access
Corneliu Toader,

Călin Petru Tătaru,

Octavian Munteanu

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(23), P. 12613 - 12613

Published: Nov. 24, 2024

Neurodegenerative diseases, such as Alzheimer's, Parkinson's, ALS, and Huntington's, remain formidable challenges in medicine, with their relentless progression limited therapeutic options. These diseases arise from a web of molecular disturbances-misfolded proteins, chronic neuroinflammation, mitochondrial dysfunction, genetic mutations-that slowly dismantle neuronal integrity. Yet, recent scientific breakthroughs are opening new paths to intervene these once-intractable conditions. This review synthesizes the latest insights into underlying dynamics neurodegeneration, revealing how intertwined pathways drive course diseases. With an eye on most promising advances, we explore innovative therapies emerging cutting-edge research: nanotechnology-based drug delivery systems capable navigating blood-brain barrier, gene-editing tools like CRISPR designed correct harmful variants, stem cell strategies that not only replace lost neurons but foster neuroprotective environments. Pharmacogenomics is reshaping treatment personalization, enabling tailored align individual profiles, while diagnostics biomarkers ushering era early, precise disease detection. Furthermore, novel perspectives gut-brain axis sparking interest mounting evidence suggests microbiome modulation may play role reducing neuroinflammatory responses linked neurodegenerative progression. Taken together, advances signal shift toward comprehensive, personalized approach could transform care. By integrating techniques, this offers forward-looking perspective future where treatments aim just manage symptoms fundamentally alter progression, presenting renewed hope for improved patient outcomes.

Language: Английский

Citations

4
Ferroptosis in Neurons: A Bibliometric Analysis of Research Trends, Key Contributions, and Emerging Directions DOI Creative Commons
Shanshan Sun,

Q Q Wang,

Ziyi Zhang

et al.

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 17, 2025

Abstract Background Neurons are the fundamental structural and functional units of nervous system, serving as core cells for information transmission regulation. They closely associated with various neurological diseases. Recent studies have shown significant advancements in research on ferroptosis neurons; however, there has been a lack bibliometric analysis this field. This study aims to provide comprehensive overview knowledge structure related neurons through methods, identify current trends hotspots, predict potential future directions. Methods We conducted search publications from 2014 2024 Web Science Core Collection (WoSCC) database. Bibliometric methods were employed analyze authors, institutions, countries, journals, references using VOSviewer, CiteSpace, R package "bibliometrix". Results included 685 articles 50 China United States being leading contributors. The number year-on-year increase. primary institutions Central South University, Harbin Medical University Melbourne. Free Radical Biology Medicine is most popular journal field, while Cell highest citation count. A total 4,673 authors contributed research, David Devos Ashley I. Bush having publications, Scott J. Dixon had co-citations. Keyword revealed that molecular mechanisms its application diseases focuses Conclusion first summarizing developments neurons. outlines predicts global hotspots trends, providing valuable scholars studying ferroptosis.

Language: Английский

Citations

0
Palmitoylation-related gene ZDHHC22 as a potential diagnostic and immunomodulatory target in Alzheimer’s disease: insights from machine learning analyses and WGCNA DOI Creative Commons

Sanying Mao,

Xiyao Zhao,

Lei Wang

et al.

European journal of medical research, Journal Year: 2025, Volume and Issue: 30(1)

Published: Jan. 22, 2025

The mechanism of palmitoylation in the pathogenesis Alzheimer's disease (AD) remains unclear. This study retrieved AD data sets from GEO database to identify palmitoylation-associated genes (PRGs). applied WGCNA along with three machine learning algorithms—random forest, LASSO regression, and SVM–RFE—to further select key PRGs (KPRGs). diagnostic performance KPRGs was evaluated using Receiver Operating Characteristic (ROC) curve analysis. Immune cell infiltration analysis conducted assess correlations between immune types, a competing endogenous RNA (ceRNA) regulatory network constructed explore their potential mechanisms. 17 were identified sets, 7 showing increased expression 10 decreased expression. Through analyses, ZDHHC22 selected as KPRG. ROC demonstrated that had an area under value 0.659, indicating moderate potential. revealed significant associations several including naïve B cells, CD8 + T M1 macrophages. In addition, 25 miRNAs 55 lncRNAs predicted potentially target ZDHHC22, forming basis for lncRNA–miRNA–mRNA ceRNA network. is first use bioinformatics methods KPRG AD, highlighting its role diagnosis regulation. provides new insights into molecular mechanisms lays foundation future targeted therapeutic strategies.

Language: Английский

Citations

0