Ageing Research Reviews最新文献_第9页

Deciphering the role of miRNAs in Alzheimer's disease: Predictive targeting and pathway modulation – A systematic review 解读 miRNAs 在阿尔茨海默病中的作用：预测性靶向和通路调节--系统综述。

IF 12.5 1区医学

Ageing Research Reviews Pub Date : 2024-09-03 DOI: 10.1016/j.arr.2024.102483

Monika Sharma , Pankaj Pal , Sukesh Kumar Gupta

{"title":"Deciphering the role of miRNAs in Alzheimer's disease: Predictive targeting and pathway modulation – A systematic review","authors":"Monika Sharma , Pankaj Pal , Sukesh Kumar Gupta","doi":"10.1016/j.arr.2024.102483","DOIUrl":"10.1016/j.arr.2024.102483","url":null,"abstract":"<div><p>Alzheimer's Disease (AD), a multifaceted neurodegenerative disorder, is increasingly understood through the regulatory lens of microRNAs (miRNAs). This review comprehensively examines the pivotal roles of miRNAs in AD pathogenesis, shedding light on their influence across various pathways. We delve into the biogenesis and mechanisms of miRNAs, emphasizing their significant roles in brain function and regulation. The review then navigates the complex landscape of AD pathogenesis, identifying key genetic, environmental, and molecular factors, with a focus on hallmark pathological features like amyloid-beta accumulation and tau protein hyperphosphorylation. Central to our discussion is the intricate involvement of miRNAs in these processes, highlighting their altered expression patterns in AD and subsequent functional implications, from amyloid-beta metabolism to tau pathology, neuroinflammation, oxidative stress, and synaptic dysfunction. The predictive analysis of miRNA targets using computational methods, complemented by experimental validations, forms a crucial part of our discourse, unraveling the contributions of specific miRNAs to AD. Moreover, we explore the therapeutic potential of miRNAs as biomarkers and in miRNA-based interventions, while addressing the challenges in translating these findings into clinical practice. This review aims to enhance understanding of miRNAs in AD, offering a foundation for future research directions and novel therapeutic strategies.</p></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"101 ","pages":"Article 102483"},"PeriodicalIF":12.5,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142142001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dysfunctional mitochondria in age-related neurodegeneration: Utility of melatonin as an antioxidant treatment 与年龄有关的神经退行性病变中的线粒体功能失调：褪黑激素作为抗氧化剂治疗的效用

IF 12.5 1区医学

Ageing Research Reviews Pub Date : 2024-09-03 DOI: 10.1016/j.arr.2024.102480

Russel J. Reiter , Ramaswamy N. Sharma , Walter Manucha , Sergio Rosales-Corral , Luiz Gustavo de Almieda Chuffa , Doris Loh , Francesca Luchetti , Walter Balduini , Piyarat Govitrapong

{"title":"Dysfunctional mitochondria in age-related neurodegeneration: Utility of melatonin as an antioxidant treatment","authors":"Russel J. Reiter , Ramaswamy N. Sharma , Walter Manucha , Sergio Rosales-Corral , Luiz Gustavo de Almieda Chuffa , Doris Loh , Francesca Luchetti , Walter Balduini , Piyarat Govitrapong","doi":"10.1016/j.arr.2024.102480","DOIUrl":"10.1016/j.arr.2024.102480","url":null,"abstract":"<div><p>Mitochondria functionally degrade as neurons age. Degenerative changes cause inefficient oxidative phosphorylation (OXPHOS) and elevated electron leakage from the electron transport chain (ETC) promoting increased intramitochondrial generation of damaging reactive oxygen and reactive nitrogen species (ROS and RNS). The associated progressive accumulation of molecular damage causes an increasingly rapid decline in mitochondrial physiology contributing to aging. Melatonin, a multifunctional free radical scavenger and indirect antioxidant, is synthesized in the mitochondrial matrix of neurons. Melatonin reduces electron leakage from the ETC and elevates ATP production; it also detoxifies ROS/RNS and via the SIRT3/FOXO pathway it upregulates activities of superoxide dismutase 2 and glutathione peroxidase. Melatonin also influences glucose processing by neurons. In neurogenerative diseases, neurons often adopt Warburg-type metabolism which excludes pyruvate from the mitochondria causing reduced intramitochondrial acetyl coenzyme A production. Acetyl coenzyme A supports the citric acid cycle and OXPHOS. Additionally, acetyl coenzyme A is a required co-substrate for arylalkylamine-N-acetyl transferase, which rate limits melatonin synthesis; therefore, melatonin production is diminished in cells that experience Warburg-type metabolism making mitochondria more vulnerable to oxidative stress. Moreover, endogenously produced melatonin diminishes during aging, further increasing oxidative damage to mitochondrial components. More normal mitochondrial physiology is preserved in aging neurons with melatonin supplementation.</p></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"101 ","pages":"Article 102480"},"PeriodicalIF":12.5,"publicationDate":"2024-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1568163724002988/pdfft?md5=dbf486b794b376c9020e1bd5629e0f3b&pid=1-s2.0-S1568163724002988-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142142002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Target modulation of glycolytic pathways as a new strategy for the treatment of neuroinflammatory diseases 靶向调节糖酵解途径作为治疗神经炎性疾病的新策略。

IF 12.5 1区医学

Ageing Research Reviews Pub Date : 2024-09-02 DOI: 10.1016/j.arr.2024.102472

Hanlong Wang , Shasha Liu , Yang Sun , Chen Chen , Ziyi Hu , Qinqin Li , Junpeng Long , Qian Yan , Jinping Liang , Yuting Lin , Songwei Yang , Meiyu Lin , Xuan Liu , Huiqin Wang , Jingbo Yu , Fan Yi , Yong Tan , Yantao Yang , Naihong Chen , Qidi Ai

{"title":"Target modulation of glycolytic pathways as a new strategy for the treatment of neuroinflammatory diseases","authors":"Hanlong Wang , Shasha Liu , Yang Sun , Chen Chen , Ziyi Hu , Qinqin Li , Junpeng Long , Qian Yan , Jinping Liang , Yuting Lin , Songwei Yang , Meiyu Lin , Xuan Liu , Huiqin Wang , Jingbo Yu , Fan Yi , Yong Tan , Yantao Yang , Naihong Chen , Qidi Ai","doi":"10.1016/j.arr.2024.102472","DOIUrl":"10.1016/j.arr.2024.102472","url":null,"abstract":"<div><p>Neuroinflammation is an innate and adaptive immune response initiated by the release of inflammatory mediators from various immune cells in response to harmful stimuli. While initially beneficial and protective, prolonged or excessive neuroinflammation has been identified in clinical and experimental studies as a key pathological driver of numerous neurological diseases and an accelerant of the aging process. Glycolysis, the metabolic process that converts glucose to pyruvate or lactate to produce adenosine 5′-triphosphate (ATP), is often dysregulated in many neuroinflammatory disorders and in the affected nerve cells. Enhancing glucose availability and uptake, as well as increasing glycolytic flux through pharmacological or genetic manipulation of glycolytic enzymes, has shown potential protective effects in several animal models of neuroinflammatory diseases. Modulating the glycolytic pathway to improve glucose metabolism and ATP production may help alleviate energy deficiencies associated with these conditions. In this review, we examine six neuroinflammatory diseases—stroke, Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), and depression—and provide evidence supporting the role of glycolysis in their treatment. We also explore the potential link between inflammation-induced aging and glycolysis. Additionally, we briefly discuss the critical role of glycolysis in three types of neuronal cells—neurons, microglia, and astrocytes—within physiological processes. This review highlights the significance of glycolysis in the pathology of neuroinflammatory diseases and its relevance to the aging process.</p></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"101 ","pages":"Article 102472"},"PeriodicalIF":12.5,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142134713","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Deciphering the microbial map and its implications in the therapeutics of neurodegenerative disorder 解密微生物图谱及其对神经退行性疾病治疗的影响。

IF 12.5 1区医学

Ageing Research Reviews Pub Date : 2024-09-01 DOI: 10.1016/j.arr.2024.102466

Shrutikirti Vashishth , Rashmi K. Ambasta , Pravir Kumar

{"title":"Deciphering the microbial map and its implications in the therapeutics of neurodegenerative disorder","authors":"Shrutikirti Vashishth , Rashmi K. Ambasta , Pravir Kumar","doi":"10.1016/j.arr.2024.102466","DOIUrl":"10.1016/j.arr.2024.102466","url":null,"abstract":"<div><p>Every facet of biological anthropology, including development, ageing, diseases, and even health maintenance, is influenced by gut microbiota’s significant genetic and metabolic capabilities. With current advancements in sequencing technology and with new culture-independent approaches, researchers can surpass older correlative studies and develop mechanism-based studies on microbiome-host interactions. The microbiota-gut-brain axis (MGBA) regulates glial functioning, making it a possible target for the improvement of development and advancement of treatments for neurodegenerative diseases (NDDs). The gut-brain axis (GBA) is accountable for the reciprocal communication between the gastrointestinal and central nervous system, which plays an essential role in the regulation of physiological processes like controlling hunger, metabolism, and various gastrointestinal functions. Lately, studies have discovered the function of the gut microbiome for brain health—different microbiota through different pathways such as immunological, neurological and metabolic pathways. Additionally, we review the involvement of the neurotransmitters and the gut hormones related to gut microbiota. We also explore the MGBA in neurodegenerative disorders by focusing on metabolites. Further, targeting the blood-brain barrier (BBB), intestinal barrier, meninges, and peripheral immune system is investigated. Lastly, we discuss the therapeutics approach and evaluate the pre-clinical and clinical trial data regarding using prebiotics, probiotics, paraprobiotics, fecal microbiota transplantation, personalised medicine, and natural food bioactive in NDDs. A comprehensive study of the GBA will felicitate the creation of efficient therapeutic approaches for treating different NDDs.</p></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"100 ","pages":"Article 102466"},"PeriodicalIF":12.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142094286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Stroke studies in large animals: Prospects of mitochondrial transplantation and enhancing efficiency using hydrogels and nanoparticle-assisted delivery 大型动物中风研究：线粒体移植的前景以及利用水凝胶和纳米颗粒辅助输送提高效率。

IF 12.5 1区医学

Ageing Research Reviews Pub Date : 2024-09-01 DOI: 10.1016/j.arr.2024.102469

Oner Ulger , Ismail Eş , Christopher M. Proctor , Oktay Algin

{"title":"Stroke studies in large animals: Prospects of mitochondrial transplantation and enhancing efficiency using hydrogels and nanoparticle-assisted delivery","authors":"Oner Ulger , Ismail Eş , Christopher M. Proctor , Oktay Algin","doi":"10.1016/j.arr.2024.102469","DOIUrl":"10.1016/j.arr.2024.102469","url":null,"abstract":"<div><p>One of the most frequent reasons for mortality and disability today is acute ischemic stroke, which occurs by an abrupt disruption of cerebral circulation. The intricate damage mechanism involves several factors, such as inflammatory response, disturbance of ion balance, loss of energy production, excessive reactive oxygen species and glutamate release, and finally, neuronal death. Stroke research is now carried out using several experimental models and potential therapeutics. Furthermore, studies are being conducted to address the shortcomings of clinical care. A great deal of research is being done on novel pharmacological drugs, mitochondria targeting compounds, and different approaches including brain cooling and new technologies. Still, there are many unanswered questions about disease modeling and treatment strategies. Before these new approaches may be used in therapeutic settings, they must first be tested on large animals, as most of them have been done on rodents. However, there are several limitations to large animal stroke models used for research. In this review, the damage mechanisms in acute ischemic stroke and experimental acute ischemic stroke models are addressed. The current treatment approaches and promising experimental methods such as mitochondrial transplantation, hydrogel-based interventions, and strategies like mitochondria encapsulation and chemical modification, are also examined in this work.</p></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"100 ","pages":"Article 102469"},"PeriodicalIF":12.5,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142082905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Recent advancement in understanding of Alzheimer's disease: Risk factors, subtypes, and drug targets and potential therapeutics 了解阿尔茨海默病的最新进展：风险因素、亚型、药物靶点和潜在疗法。

IF 12.5 1区医学

Ageing Research Reviews Pub Date : 2024-08-31 DOI: 10.1016/j.arr.2024.102476

Sneh Prabha , Mohd Sajad , Gulam Mustafa Hasan , Asimul Islam , Md Imtaiyaz Hassan , Sonu Chand Thakur

{"title":"Recent advancement in understanding of Alzheimer's disease: Risk factors, subtypes, and drug targets and potential therapeutics","authors":"Sneh Prabha , Mohd Sajad , Gulam Mustafa Hasan , Asimul Islam , Md Imtaiyaz Hassan , Sonu Chand Thakur","doi":"10.1016/j.arr.2024.102476","DOIUrl":"10.1016/j.arr.2024.102476","url":null,"abstract":"<div><p>Alzheimer's disease (AD) is a significant neocortical degenerative disorder characterized by the progressive loss of neurons and secondary alterations in white matter tracts. Understanding the risk factors and mechanisms underlying AD is crucial for developing effective treatments. The risk factors associated with AD encompass a wide range of variables, including gender differences, family history, and genetic predispositions. Additionally, environmental factors such as air pollution and lifestyle-related conditions like cardiovascular disease, gut pathogens, and liver pathology contribute substantially to the development and progression of AD and its subtypes. This review provides current update and deeper insights into the role of diverse risk factors, categorizing AD into its distinct subtypes and elucidating their specific pathophysiological mechanisms. Unlike previous studies that often focus on isolated aspects of AD, our review integrates these factors to offer a comprehensive understanding of the disease. Furthermore, the review explores a variety of drug targets linked to the neuropathology of different AD subtypes, highlighting the potential for targeted therapeutic interventions. We further discussed the novel therapeutic options and categorized them according to their targets. The roles of different drug targets were comprehensively studied, and the mechanism of action of their inhibitors was discussed in detail. By comprehensively covering the interplay of risk factors, subtype differentiation, and drug targets, this review provides a deeper understanding of AD and suggests directions for future research and therapeutic strategies.</p></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"101 ","pages":"Article 102476"},"PeriodicalIF":12.5,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142121309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Structural and functional remodeling of neural networks in β-amyloid driven hippocampal hyperactivity β-淀粉样蛋白驱动的海马过度活跃神经网络的结构和功能重塑

IF 12.5 1区医学

Ageing Research Reviews Pub Date : 2024-08-31 DOI: 10.1016/j.arr.2024.102468

Jinquan Li , Yanjun Liu , Chuhui Yin, Yan Zeng, Yufei Mei

{"title":"Structural and functional remodeling of neural networks in β-amyloid driven hippocampal hyperactivity","authors":"Jinquan Li , Yanjun Liu , Chuhui Yin, Yan Zeng, Yufei Mei","doi":"10.1016/j.arr.2024.102468","DOIUrl":"10.1016/j.arr.2024.102468","url":null,"abstract":"<div><p>Early detection of Alzheimer’s disease (AD) is essential for improving the patients outcomes and advancing our understanding of disease, allowing for timely intervention and treatment. However, accurate biomarkers are still lacking. Recent evidence indicates that hippocampal hyperexcitability precedes the diagnosis of AD decades ago, can predict cognitive decline. Thus, could hippocampal hyperactivity be a robust biomarker for early-AD, and what drives hippocampal hyperactivity in early-AD? these critical questions remain to be answered. Increasing clinical and experimental studies suggest that early hippocampal activation is closely associated with longitudinal β-amyloid (Aβ) accumulation, Aβ aggregates, in turn, enhances hippocampal activity. Therefore, in this narrative review, we discuss the role of Aβ-induced altered intrinsic neuronal properties as well as structural and functional remodeling of glutamatergic, GABAergic, cholinergic, noradrenergic, serotonergic circuits in hippocampal hyperactivity. In addition, we analyze the available therapies and trials that can potentially be used clinically to attenuate hippocampal hyperexcitability in AD. Overall, the present review sheds lights on the mechanism behind Aβ-induced hippocampal hyperactivity, and highlights that hippocampal hyperactivity could be a robust biomarker and therapeutic target in prodromal AD.</p></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"101 ","pages":"Article 102468"},"PeriodicalIF":12.5,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142115810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Investigating the research trajectory and future trends of immune disorders in diabetes cardiovascular complications: A bibliometric analysis over the past decade based on big data 糖尿病心血管并发症中免疫紊乱的研究轨迹及未来趋势调查：基于大数据的过去十年文献计量分析。

IF 12.5 1区医学

Ageing Research Reviews Pub Date : 2024-08-31 DOI: 10.1016/j.arr.2024.102473

Xinglei Li , Zhou Xu , Tieqiu Huang , Yixin Jiang , Huan Wan , Deju Zhang , Jitao Ling , Yuting Wu , Xiao Liu , Pingping Yang , Linhua Fu , Jianping Liu , Jing Zhang , Peng Yu

{"title":"Investigating the research trajectory and future trends of immune disorders in diabetes cardiovascular complications: A bibliometric analysis over the past decade based on big data","authors":"Xinglei Li , Zhou Xu , Tieqiu Huang , Yixin Jiang , Huan Wan , Deju Zhang , Jitao Ling , Yuting Wu , Xiao Liu , Pingping Yang , Linhua Fu , Jianping Liu , Jing Zhang , Peng Yu","doi":"10.1016/j.arr.2024.102473","DOIUrl":"10.1016/j.arr.2024.102473","url":null,"abstract":"<div><h3>Introduction</h3><p>Cardiovascular complications of diabetes are a top cause of death in diabetics and often involve immune system problems. Despite numerous studies, there's a shortage of extensive data to advance this field. This study aims to systematically analyze the role of immune dysregulation in these complications using bibliometric methods, to outline the research path and predict future directions.</p></div><div><h3>Methods</h3><p>Published from January 1, 2014 to December 31, 2023, 2826 records from the Web of Science Core Collection were analyzed. Collaboration networks, keyword co-occurrences, references, and research hotspots were visualized and analyzed using Microsoft Office Excel 2019, VOSviewer, CiteSpace, and R software.</p></div><div><h3>Results</h3><p>The number of research papers and citations on this topic has been increasing from 2014 to 2023, with significant contributions from the United States and China. Studies have focused on the effects of oxidative stress, inflammation, metabolism, gut microbiota, and COVID-19 on diabetic heart problems, highlighting the role of immune dysregulation in these diseases.</p></div><div><h3>Conclusion</h3><p>This research provides an overview of immune dysregulation in the cardiovascular complications of diabetes, explores potential treatments including immunomodulation, insulin resistance, and the benefits of vitamin D on cardiovascular disease, and helps advance the field.</p></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"101 ","pages":"Article 102473"},"PeriodicalIF":12.5,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142121307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Emerging microglial biology highlights potential therapeutic targets for Alzheimer's disease 新出现的小胶质细胞生物学特性凸显了阿尔茨海默病的潜在治疗靶点。

IF 12.5 1区医学

Ageing Research Reviews Pub Date : 2024-08-31 DOI: 10.1016/j.arr.2024.102471

Xi Fan , Hui Chen , Wei He , Jianmin Zhang

{"title":"Emerging microglial biology highlights potential therapeutic targets for Alzheimer's disease","authors":"Xi Fan , Hui Chen , Wei He , Jianmin Zhang","doi":"10.1016/j.arr.2024.102471","DOIUrl":"10.1016/j.arr.2024.102471","url":null,"abstract":"<div><p>Alzheimer's disease is a chronic degenerative disease of the central nervous system, which primarily affects elderly people and accounts for 70–80 % of dementia cases. The current prevailing amyloid cascade hypothesis suggests that Alzheimer’s disease begins with the deposition of amyloid β (Aβ) in the brain. Major therapeutic strategies target Aβ production, aggregation, and clearance, although many clinical trials have shown that these therapeutic strategies are not sufficient to completely improve cognitive deficits in AD patients. Recent genome-wide association studies have identified that multiple important regulators are the most significant genetic risk factors for Alzheimer's disease, especially in the innate immune pathways. These genetic risk factors suggest a critical role for microglia, highlighting their therapeutic potential in treating neurodegenerative diseases. In this review, we discuss how these recently documented AD risk genes affect microglial function and AD pathology and how they can be further targeted to regulate microglial states and slow AD progression, especially the highly anticipated APOE and TREM2 targets. We focused on recent findings that modulation of innate and adaptive neuroimmune microenvironment crosstalk reverses cognitive deficits in AD patients. We also considered novel strategies for microglia in AD patients.</p></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"101 ","pages":"Article 102471"},"PeriodicalIF":12.5,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142115798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Ferroptosis in Parkinson's disease —— The iron-related degenerative disease 帕金森病--与铁有关的退行性疾病中的铁沉积症。

IF 12.5 1区医学

Ageing Research Reviews Pub Date : 2024-08-31 DOI: 10.1016/j.arr.2024.102477

Zhengyang Yao , Qian Jiao , Xixun Du , Fengju Jia , Xi Chen , Chunling Yan , Hong Jiang

引用次数: 0