Ageing Research Reviews最新文献

{"title":"Progress in the mechanisms of pain associated with neurodegenerative diseases","authors":"Zhicheng Tian ,&nbsp;Qi Zhang ,&nbsp;Ling Wang ,&nbsp;Mengxiang Li ,&nbsp;Tianjing Li ,&nbsp;Yujie Wang ,&nbsp;Zixuan Cao ,&nbsp;Xiaofan Jiang ,&nbsp;Peng Luo","doi":"10.1016/j.arr.2024.102579","DOIUrl":"10.1016/j.arr.2024.102579","url":null,"abstract":"<div><div>Neurodegenerative diseases (NDDs) represent a class of neurological disorders characterized by the progressive degeneration or loss of neurons, impacting millions of individuals globally. In addition to the typical manifestations, pain is a prevalent symptom associated with NDDs, seriously impacting the quality of life for patients. The pathogenesis of pain associated with NDDs is intricate and multifaceted. Currently, the clinical management of NDDs-related pain symptoms predominantly relies on conventional pharmacological agents or physical therapy. However, these approaches often fail to produce satisfactory outcomes. This article summarizes the underlying mechanisms of major NDDs-associated pain: Neuroinflammation, Brain and spinal cord dysfunctions, Mitochondrial dysfunction, Risk gene and pathological protein, as well as Receptor, channel, and neurotransmitter. While numerous studies have investigated the downstream pathological processes associated with these mechanisms, there remains a significant gap in identifying the key initiating factors. Specifically, there is insufficient evidence for the upstream elements that activate microglia and astrocytes in neuroinflammation leading to pain in NDDs. Likewise, there is an absence of upstream factors elucidating how dysfunctions in the brain and spinal cord, as well as mitochondrial impairments, contribute to the development of pain. Furthermore, the specific mechanisms through which hallmark pathological proteins related to NDDs contribute to these pathological processes remain inadequately understood. The objective of this article is to synthesize the existing mechanisms underlying pain associated with NDDs, including Alzheimer's disease, Parkinson's disease, Huntington's disease, Schizophrenia, Amyotrophic lateral sclerosis, and Multiple sclerosis, while also identifying gaps and deficiencies in these mechanisms. This paper offers insights for future research trajectories. Given the intricate pathogenesis of NDDs-related pain, it emphasizes that a promising short-term strategy is combination therapy—intervening concurrently in multiple pathological processes—akin to the cocktail approach utilized in treating acquired immunodeficiency syndrome (AIDS). For long-term advancements, achieving breakthroughs in the treatment of the NDDs themselves will remain essential for alleviating accompanying pain symptoms.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"102 ","pages":"Article 102579"},"PeriodicalIF":12.5,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634249","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}

{"title":"Non-canonical pathways associated to Amyloid beta and tau protein dyshomeostasis in Alzheimer’s disease: A narrative review","authors":"Anna Maggiore ,&nbsp;Valentina Latina ,&nbsp;Maria D’Erme ,&nbsp;Giuseppina Amadoro ,&nbsp;Roberto Coccurello","doi":"10.1016/j.arr.2024.102578","DOIUrl":"10.1016/j.arr.2024.102578","url":null,"abstract":"<div><div>Alzheimer’s Disease (AD) is the most common form of dementia among elderly people. This disease imposes a significant burden on the healthcare system, society, and economy due to the increasing global aging population. Current trials with drugs or bioactive compounds aimed at reducing cerebral Amyloid beta (Aβ) plaques and tau protein neurofibrillary tangles, which are the two main hallmarks of this devastating neurodegenerative disease, have not provided significant results in terms of their neuropathological outcomes nor met the expected clinical end-points. Ageing, genetic and environmental risk factors, along with different clinical symptoms suggest that AD is a complex and heterogeneous disorder with multiple interconnected pathological pathways rather than a single disease entity. In the present review, we highlight and discuss various non-canonical, Aβ-independent mechanisms, like gliosis, unhealthy dietary intake, lipid and sugar signaling, and cerebrovascular damage that contribute to the onset and development of AD. We emphasize that challenging the traditional “amyloid cascade hypothesis” may improve our understanding of this age-related complex syndrome and help fight the progressive cognitive decline in AD.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"102 ","pages":"Article 102578"},"PeriodicalIF":12.5,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634231","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}

{"title":"Mitochondrial dysfunction as a therapeutic strategy for neurodegenerative diseases: Current insights and future directions","authors":"Ying-ying Gu ,&nbsp;Xin-ru Zhao ,&nbsp;Nan Zhang ,&nbsp;Yuan Yang ,&nbsp;Ying Yi ,&nbsp;Qian-hang Shao ,&nbsp;Ming-xuan Liu ,&nbsp;Xiao-ling Zhang","doi":"10.1016/j.arr.2024.102577","DOIUrl":"10.1016/j.arr.2024.102577","url":null,"abstract":"<div><div>Neurodegenerative diseases, as common diseases in the elderly, tend to become younger due to environmental changes, social development and other factors. They are mainly characterized by progressive loss or dysfunction of neurons in the central or peripheral nervous system, and common diseases include Parkinson's disease, Alzheimer's disease, Huntington's disease and so on. Mitochondria are important organelles for adenosine triphosphate (ATP) production in the brain. In recent years, a large amount of evidence has shown that mitochondrial dysfunction plays a direct role in neurodegenerative diseases, which is expected to provide new ideas for the treatment of related diseases. This review will summarize the main mechanisms of mitochondrial dysfunction in neurodegenerative diseases, as well as collating recent advances in the study of mitochondrial disorders and new therapies.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"102 ","pages":"Article 102577"},"PeriodicalIF":12.5,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634254","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}

{"title":"Priorities in tackling noncommunicable diseases among the population aged 60 years and older in China, 1990–2021: A population-based study","authors":"Yi Dai ,&nbsp;Di Teng ,&nbsp;Chengshuo Zhang ,&nbsp;Haoyu Wang ,&nbsp;Yaxin Lai ,&nbsp;Shuangning Ding ,&nbsp;Yang Han ,&nbsp;Lei Dou ,&nbsp;Shize Yang ,&nbsp;Yue Ma ,&nbsp;Bingyang Liu ,&nbsp;Ziyu Gao ,&nbsp;Liang He ,&nbsp;Xu Han ,&nbsp;Guofeng Zhang ,&nbsp;Qiaobei Li ,&nbsp;Qinghong Zeng ,&nbsp;Hangjia Liu ,&nbsp;Haoran Zhou ,&nbsp;Siyu Wang ,&nbsp;Yongze Li","doi":"10.1016/j.arr.2024.102574","DOIUrl":"10.1016/j.arr.2024.102574","url":null,"abstract":"<div><h3>Objective</h3><div>In China, it is expected that every one in three people will be aged 60 years and above in 2040, surpassing other low- and middle-income countries. The noncommunicable disease (NCD) burden and trends among elderly people must be clarified.</div></div><div><h3>Methods</h3><div>In this trend analysis based on the Global Burden of Diseases Study 2021, we reported NCDs per 100,000 people and average annual percentage changes (AAPCs) in disability-adjusted life-years (DALYs), mortality, and incidence at three levels of the GBD 2021 hierarchy by age subgroups and by sex in the older population aged 60 years and above in China during 1990–2021.</div></div><div><h3>Results</h3><div>In 2021, there were 382 million incident cases of NCDs among elderly individuals in China, leading to 201 million DALYs and 9 million deaths in the same year. During 1990–2021, although cardiovascular diseases substantially reduced both DALYs (-1.2 %/year) and mortality (-1.08 %/year), cardiovascular diseases still accounted for the greatest percentage of DALYs (31000 per 100,000 population [95 % UI 26071–35908]) and mortality (2025 [1678–2355]) in 2021. During 1990–2021, while the total incidence of NCDs decreased (-0.01 %/year), the incidence of mental disorders (0.68 %/year) rapidly increased. Among all level 3 causes, depressive disorder caused the greatest increases in DALYs (0.74%/year), while chronic respiratory diseases showed the most rapid decreases in both DALYs (-3.6 %/year) and mortality (-3.6 %/year). The priorities of NCD control in each age subgroup and sex among elderly individuals varied. In 2021, males had a greater DALY rate from NCDs per 100,000 people than females did (96409 [95 % UI 80625–112283] vs. 67112 [56878–77547]), but females had a greater incidence rate of NCDs than males did (150276 [139285–163373]) vs. 137571 [127439–148789]). High systolic blood pressure had surpassed household air pollution from solid fuels as the leading risk factor for DALYs among the elderly, and it continued to be the top risk factor for mortality in this population.</div></div><div><h3>Conclusions</h3><div>The total NCD burden among elderly people in China has been decreasing and changing. Substantial reductions in cardiovascular diseases and chronic respiratory disease have been observed, while rapid increases in mental disorders has also been found. Policies need to be updated to reflect the changing risk landscape. Target interventions should consider age subgroups and sex differences among this population.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"102 ","pages":"Article 102574"},"PeriodicalIF":12.5,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634269","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}

{"title":"Iron homeostasis and neurodegeneration in the ageing brain: Insight into ferroptosis pathways","authors":"Mohammed Alrouji ,&nbsp;Saleha Anwar ,&nbsp;Kumar Venkatesan ,&nbsp;Moyad Shahwan ,&nbsp;Md Imtaiyaz Hassan ,&nbsp;Asimul Islam ,&nbsp;Anas Shamsi","doi":"10.1016/j.arr.2024.102575","DOIUrl":"10.1016/j.arr.2024.102575","url":null,"abstract":"<div><div>Ageing is a major risk factor for various chronic diseases and offers a potential target for developing novel and broadly effective preventatives or therapeutics for age-related conditions, including those affecting the brain. Mechanisms contributing to ageing have been summarized as the hallmarks of ageing, with iron imbalance being one of the major factors. Ferroptosis, an iron-mediated lipid peroxidation-induced programmed cell death, has recently been implicated in neurodegenerative diseases such as Alzheimer’s disease (AD), Parkinson’s disease (PD) and Huntington’s disease (HD). Addressing ferroptosis offers both opportunities and challenges for treating neurodegenerative diseases, though the specific mechanisms remain unclear. This research explores the key processes behind how ferroptosis contributes to brain ageing, with a focus on the complex signaling networks that are involved. The current article aims to uncover that how ferroptosis, a specific type of cell death, may drive age-related changes in the brain. Additionally, the article also unveils its role in neurodegenerative diseases, discussing how understanding these mechanisms could open up new therapeutic avenues.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"102 ","pages":"Article 102575"},"PeriodicalIF":12.5,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142634253","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}

{"title":"14–3-3 protein and its isoforms: A common diagnostic marker for Alzheimer’s disease, Parkinson’s disease and glaucomatous neurodegeneration","authors":"Siva Prasad Panda ,&nbsp;Adarsh Kesharwani ,&nbsp;Bhoopendra Singh ,&nbsp;Arya Lakshmi Marisetti ,&nbsp;MVNL Chaitanya ,&nbsp;Saurabh Dahiya ,&nbsp;S. Ponnusankar ,&nbsp;Sanjesh Kumar ,&nbsp;Mansi Singh ,&nbsp;Praveen Kumar Shakya ,&nbsp;P.Dharani Prasad ,&nbsp;Ajay Guru","doi":"10.1016/j.arr.2024.102572","DOIUrl":"10.1016/j.arr.2024.102572","url":null,"abstract":"<div><div>There is a molecular coupling between neurodegenerative diseases, including glaucomatous neurodegeneration (GN), Alzheimer's disease (AD), and Parkinson's disease (PD). Many cells in the eye and the brain have the right amount of 14–3–3 proteins (14–3–3 s) and their isoforms, such as β, ε, γ, η, θ, π, and γ. These cells include keratocytes, endothelial cells, corneal epithelial cells, and primary conjunctival epithelial cells. 14–3–3 s regulate autophagy and mitophagy, help break down built-up proteins, and connect to other proteins to safeguard against neurodegeneration in AD, PD, GN, and glioblastoma. By interacting with these proteins, 14–3–3 s stop Bad and Bax proteins from entering mitochondria and make them less effective. These interactions inhibit neuronal apoptosis. They play many important roles in managing the breakdown of lysosomal proteins, tau, and Aβ, which is why the 14–3–3 s could be used as therapeutic targets in AD. Furthermore, researchers have discovered 14–3–3 s in Lewy bodies, which are associated with various proteins like LRRK2, ASN, and Parkin, all of which play a role in developing Parkinson's disease (PD). The 14–3–3 s influence the premature aging and natural wrinkles of human skin. Studies have shown that lowering 14–3–3 s in the brain can lead to an increase in cell-death proteins like BAX and ERK, which in turn causes excitotoxicity-induced neurodegeneration. This review aimed to clarify the role of 14–3–3 s in the neuropathology of AD, PD, and GN, as well as potential diagnostic markers for improving neuronal survival and repair.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"102 ","pages":"Article 102572"},"PeriodicalIF":12.5,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142570148","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}

{"title":"Gut microbiome and Alzheimer’s disease: What we know and what remains to be explored","authors":"Bhupinder Kapoor ,&nbsp;Pratim Biswas ,&nbsp;Monica Gulati ,&nbsp;Pooja Rani ,&nbsp;Reena Gupta","doi":"10.1016/j.arr.2024.102570","DOIUrl":"10.1016/j.arr.2024.102570","url":null,"abstract":"<div><div>With advancement in human microbiome research, an increasing number of scientific evidences have endorsed the key role of gut microbiota in the pathogenesis of Alzheimer disease. Microbiome dysbiosis, characterized by altered diversity and composition, as well as rise of pathobionts influence not only various gut disorder but also central nervous system disorders such as AD. On the basis of accumulated evidences of past few years now it is quite clear that the gut microbiota can control the functions of the central nervous system (CNS) through the gut–brain axis, which provides a new prospective into the interactions between the gut and brain. The main focus of this review is on the molecular mechanism of the crosstalk between the gut microbiota and the brain through the gut–brain axis, and on the onset and development of neurological disorders triggered by the dysbiosis of gut microbiota. Due to microbiota dysbiosis the permeability of the gut and blood brain barrier is increased which may mediate or affect AD. Along with this, bacterial population of the gut microbiota can secrete amyloid proteins and lipopolysaccharides in a large quantity which may create a disturbance in the signaling pathways and the formation of proinflammatory cytokines associated with the pathogenesis of AD. These topics are followed by a critical analysis of potential intervention strategies targeting gut microbiota dysbiosis, including the use of probiotics, prebiotics, metabolites, diets and fecal microbiota transplantation. The main purpose of this review includes the summarization and discussion on the recent finding that may explain the role of the gut microbiota in the development of AD. Understanding of these fundamental mechanisms may provide a new insight into the novel therapeutic strategies for AD.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"102 ","pages":"Article 102570"},"PeriodicalIF":12.5,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142565062","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}

{"title":"Aging, brain plasticity, and motor learning","authors":"Jolien Gooijers ,&nbsp;Lisa Pauwels ,&nbsp;Melina Hehl ,&nbsp;Caroline Seer ,&nbsp;Koen Cuypers ,&nbsp;Stephan P. Swinnen","doi":"10.1016/j.arr.2024.102569","DOIUrl":"10.1016/j.arr.2024.102569","url":null,"abstract":"<div><div>Motor skill learning, the process of acquiring new motor skills, is critically important across the lifespan, from early development through adulthood and into older age, as well as in pathological conditions (i.e., rehabilitation). Extensive research has demonstrated that motor skill acquisition in young adults is accompanied by significant neuroplastic changes, including alterations in brain structure (gray and white matter), function (i.e., activity and connectivity), and neurochemistry (i.e., levels of neurotransmitters). In the aging population, motor performance typically declines, characterized by slower and less accurate movements. However, despite these age-related changes, older adults maintain the capacity for skill improvement through training. In this review, we explore the extent to which the aging brain retains the ability to adapt in response to motor learning, specifically whether skill acquisition is accompanied by neural changes. Furthermore, we discuss the associations between inter-individual variability in brain structure and function and the potential for future learning in older adults. Finally, we consider the use of non-invasive brain stimulation techniques aimed at optimizing motor learning in this population. Our review provides insights into the neurobiological underpinnings of motor learning in older adults and emphasizes strategies to enhance their motor skill acquisition.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"102 ","pages":"Article 102569"},"PeriodicalIF":12.5,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142565060","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}

{"title":"Exercise-induced adaptive response of different immune organs during ageing","authors":"Huanghao Zhou ,&nbsp;Xiao Han ,&nbsp;Chunxiu Huang ,&nbsp;Huijuan Wu ,&nbsp;Yue Hu ,&nbsp;Cong Chen ,&nbsp;Jing Tao","doi":"10.1016/j.arr.2024.102573","DOIUrl":"10.1016/j.arr.2024.102573","url":null,"abstract":"<div><div>The immune system plays a crucial role in the ageing process. As individuals age, significant alterations in the immune system experiences occur, marked by a decline in immune cell count, compromised immune function, and decreased immune regulation across various immune organs. These changes collectively weaken the capacity to combat diseases and infections, highlighting the vulnerability that accompanies ageing. Exercise is a potent intervention that profoundly influences holistic well-being and disease mitigation, with a notable emphasis on immune modulation. In general, regular moderate exercise holds significant potential to enhance immune defense mechanisms and metabolic well-being by augmenting the circulation and activation of immune cells. However, some exercise modalities would trigger detrimental effects on the immune system. It can be seen that the regulatory responses of various immune organs to diverse exercise patterns are different. This review aims to examine the immunological responses elicited by exercise across various immune organs, including the lymph nodes, spleen, bone marrow, and thymus, to underscore the nuanced interplay between exercise patterns and the immune organ. This underscores the importance of customizing exercise interventions to optimize immune function across the lifespan.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"102 ","pages":"Article 102573"},"PeriodicalIF":12.5,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142560684","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}

{"title":"Molecular mechanisms of neurofilament alterations and its application in assessing neurodegenerative disorders","authors":"Shanmukha Sreeya Devarakonda ,&nbsp;Shaik Basha ,&nbsp;Anjana Pithakumar ,&nbsp;Thoshna L B ,&nbsp;Darshan Chikkanayakanahalli Mukunda ,&nbsp;Jackson Rodrigues ,&nbsp;Ameera K ,&nbsp;Shimul Biswas ,&nbsp;Aparna Ramakrishna Pai ,&nbsp;Sushma Belurkar ,&nbsp;Krishna Kishore Mahato","doi":"10.1016/j.arr.2024.102566","DOIUrl":"10.1016/j.arr.2024.102566","url":null,"abstract":"<div><div>Neurofilaments are intermediate filaments present in neurons. These provide structural support and maintain the size and shape of the neurons. Dysregulation, mutation, and aggregation of neurofilaments raise the levels of these proteins in the blood and cerebrospinal fluid (CSF), which are characteristic features of axonal damage and certain rare neurological diseases, such as Giant Axonal Neuropathy and Charcot-Mare-Tooth disease. Understanding the structure, dynamics, and function of neurofilaments has been greatly enhanced by a diverse range of biochemical and preclinical investigations conducted over more than four decades. Recently, there has been a resurgence of interest in post-translational modifications of neurofilaments, such as phosphorylation, aggregation, mutation, oxidation, etc. Over the past twenty years, several rare disorders have been studied from structural alterations of neurofilaments. These disorders are monitored by fluid biomarkers such as neurofilament light chains. Currently, there are many tools, such as Enzyme-Linked Immunosorbent Assay, Electrochemiluminescence Assay, Single-Molecule Array, Western/immunoblotting, etc., in use to assess the neurofilament proteins in Blood and CSF. However, all these techniques utilize expensive, non-specific, or antibody-based methods, which make them unsuitable for routine screening of neurodegenerative disorders. This provides room to search for newer sensitive, cost-effective, point-of-care tools for rapid screening of the disease. For a long time, the molecular mechanisms of neurofilaments have been poorly understood due to insufficient research attempts, and a deeper understanding of them remains elusive. Therefore, this review aims to highlight the available literature on molecular mechanisms of neurofilaments and the function of neurofilaments in axonal transport, axonal conduction, axonal growth, and neurofilament aggregation, respectively. Further, this review discusses the role of neurofilaments as potential biomarkers for the identification of several neurodegenerative diseases in clinical laboratory practice.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"102 ","pages":"Article 102566"},"PeriodicalIF":12.5,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142559689","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}