Ageing Research Reviews最新文献

{"title":"Adenosine metabolism and receptors in aging of the skin, musculoskeletal, immune and cardiovascular systems","authors":"Piul Rabbani ,&nbsp;Bhama Ramkhelawon ,&nbsp;Bruce N. Cronstein","doi":"10.1016/j.arr.2025.102695","DOIUrl":"10.1016/j.arr.2025.102695","url":null,"abstract":"<div><div>Aging populations worldwide face an increasing burden of age-related chronic conditions, necessitating a deeper understanding of the underlying mechanisms. Purine metabolism has emerged as a crucial player in the pathophysiology of aging, affecting various tissues and organs. Dysregulation of purine metabolism, particularly alterations in extracellular adenosine levels and adenosine receptor signaling, contributes to age-related musculoskeletal problems, cardiovascular diseases, inflammation, and impaired immune responses. Changes in purine metabolism are associated with diminished tissue repair and regeneration, altered bone density, and impaired muscle regeneration. Mechanistically, age-related alterations in purine metabolism involve reductions in extracellular adenosine production, impaired autocrine signaling, and dysregulated expression of CD73 and CD39. Targeting adenosine receptors, such as A_2A and A_2B receptors, emerges as a promising therapeutic approach to mitigate age-related conditions, including sarcopenia, obesity, osteoarthritis, and impaired wound healing. Since we cannot reverse time, understanding the intricate molecular interplay between purine metabolism and aging-related pathologies holds significant potential for developing novel therapeutic strategies to improve the health and quality of life of aging populations. In this review, we compile the findings related to purine metabolism during aging in several tissues and organs and provide insights into how these signals can be manipulated to circumvent the deleterious effects of the passage of time on our body.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"106 ","pages":"Article 102695"},"PeriodicalIF":12.5,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143445478","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":"Association of frailty and pre-frailty with all-cause and cardiovascular mortality in diabetes: Three prospective cohorts and a meta-analysis","authors":"Lin Wen ,&nbsp;Yanhui Lu ,&nbsp;Xin Li ,&nbsp;Yu An ,&nbsp;Xiao Tan ,&nbsp;Liangkai Chen","doi":"10.1016/j.arr.2025.102696","DOIUrl":"10.1016/j.arr.2025.102696","url":null,"abstract":"<div><h3>Objective</h3><div>To investigate the association of frailty status with all-cause and cardiovascular disease (CVD) mortality in individuals with diabetes.</div></div><div><h3>Methods</h3><div>Data was sourced from the Third National Health and Nutrition Examination Survey (NHANES III, 1988–1994), NHANES (1999–2006), and the UK Biobank. Frailty status was assessed using the Fried phenotype and classified as non-frailty, pre-frailty, and frailty. We further performed a meta-analysis involving 19 prospective cohort studies (753,480 patients) to summarize the existing evidence.</div></div><div><h3>Results</h3><div>We included 31,225 diabetes patients from NHANES III (mean age 63.3 ± 0.8, 56.4 % female), NHANES 1999–2006 (mean age 61.6 ± 0.4, 49.7 % female), and the UK Biobank (mean age 59.6 ± 7.2, 39.5 % female). The prevalence of frailty was 9.9 %, 10.7 %, and 12.1 % across respective cohorts. During a follow-up period exceeding 13 years, we observed consistent results that frailty and pre-frailty were significantly associated with increased risks of all-cause and CVD mortality in diabetes. Notably, of the five domains used to assess frailty phenotypes, low gait speed showed the strongest association with all-cause and CVD mortality risks. Meta-analysis showed that, compared to non-frailty, frailty in patients with diabetes was associated with a 1.8-fold higher risk of all-cause mortality and a 2.0-fold higher risk of CVD mortality. Similarly, pre-frailty was associated with a 1.3-fold higher risk of all-cause mortality and a 1.4-fold higher risk of CVD mortality.</div></div><div><h3>Conclusions</h3><div>This study established a strong association between frailty, pre-frailty, and increased all-cause and CVD-related mortality in diabetes. Integrating frailty assessment into routine practice to identify frail and pre-frail status early on is recommended, followed by the implementation of targeted healthy lifestyle interventions to mitigate adverse outcomes.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"106 ","pages":"Article 102696"},"PeriodicalIF":12.5,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143460633","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":"Does drug repurposing bridge the gaps in management of Parkinson’s disease? Unravelling the facts and fallacies","authors":"Bushra Bashir ,&nbsp;Sukriti Vishwas ,&nbsp;Gaurav Gupta ,&nbsp;Keshav Raj Paudel ,&nbsp;Harish Dureja ,&nbsp;Puneet Kumar ,&nbsp;Hyunah Cho ,&nbsp;Vrashabh V. Sugandhi ,&nbsp;Popat S. Kumbhar ,&nbsp;John Disouza ,&nbsp;Muralikrishnan Dhanasekaran ,&nbsp;Bey Hing Goh ,&nbsp;Monica Gulati ,&nbsp;Kamal Dua ,&nbsp;Sachin Kumar Singh","doi":"10.1016/j.arr.2025.102693","DOIUrl":"10.1016/j.arr.2025.102693","url":null,"abstract":"&lt;div&gt;&lt;div&gt;Repurposing the existing drugs for the management of both common and rare diseases is increasingly appealing due to challenges such as high attrition rates, the economy, and the slow pace of discovering new drugs. Drug repurposing involves the utilization of existing medications to treat diseases for which they were not originally intended. Despite encountering scientific and economic challenges, the pharmaceutical industry is intrigued by the potential to uncover new indications for medications. Medication repurposing is applicable across different stages of drug development, with the greatest potential observed when the drug has undergone prior safety testing. In this review, strategies for repurposing drugs for Parkinson’s disease (PD) are outlined, a neurodegenerative disorder predominantly impacting dopaminergic neurons in the substantia nigra pars compacta region. PD is a debilitating neurodegenerative condition marked by an amalgam of motor and non-motor symptoms. Despite the availability of certain symptomatic treatments, particularly targeting motor symptoms, there remains a lack of established drugs capable of modifying the clinical course of PD, leading to its unchecked progression. Although standard drug discovery initiatives focusing on treatments that relieve diseases have yielded valuable understanding into the underlying mechanisms of PD, none of the numerous promising candidates identified in preclinical studies have successfully transitioned into clinically effective medications. Due to the substantial expenses associated with drug discovery endeavors, it is understandable that there has been a notable shift towards drug reprofiling strategies. Assessing the efficacy of an existing medication offers the additional advantage of circumventing the requirement for preclinical safety assessments and formulation enhancements, consequently streamlining the process and reducing both the duration of time and financial investments involved in bringing a treatment to clinical fruition. Furthermore, repurposed drugs may benefit from lower rates of failure, presenting an additional potential advantage. Various strategies for repurposing drugs are available to researchers in the field of PD. Some of these strategies have demonstrated effectiveness in identifying appropriate drugs for clinical trials, thereby providing validation for such strategies. This review provides an overview of the diverse strategies employed for drug reprofiling from approaches that place emphasis on single-gene transcriptional investigations to comprehensive epidemiological correlation analysis. Additionally, instances of previous or current research endeavors employing each strategy have been discussed. For the strategies that have not been yet implemented in PD research, their strategic efficacy is demonstrated using examples involving other disorders. In this review, we assess the safety and efficacy potential of prominent candidates repurposed as potent","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"105 ","pages":"Article 102693"},"PeriodicalIF":12.5,"publicationDate":"2025-02-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143428912","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":"cGAS-STING targeting offers novel therapeutic opportunities in neurological diseases","authors":"Hongquan Wang ,&nbsp;Joshua S. Fleishman ,&nbsp;Shuang Wu ,&nbsp;Guan Wang ,&nbsp;Lida Du ,&nbsp;Jilai Li ,&nbsp;Jichen Du","doi":"10.1016/j.arr.2025.102691","DOIUrl":"10.1016/j.arr.2025.102691","url":null,"abstract":"<div><div>Cyclic guanosine monophosphate (GMP)-adenosine monophosphate (AMP) (cGAMP) synthase (cGAS) is a cytosolic DNA sensor that produces the secondary messenger cGAMP. cGAMP activates the endoplasmic reticulum-associated adaptor stimulator of interferon genes (STING) and activates the innate immune system to produce a type I interferon response. Besides sensing microbial DNA, cGAS can also be activated by self-DNA or endogenous DNA, including that derived from genotoxic extranuclear chromatin and mitochondrially released DNA, indicating that cGAS-STING is an important mechanism in sterile inflammatory responses, autoimmunity, and cellular senescence. However, aberrant activation of the cGAS-STING pathway results in inflammatory and autoimmune diseases. cGAS-STING has emerged as a vital mechanism driving the pathogenesis of inflammation, implicating cGAS-STING signaling in neurological diseases. In this review, we first outline the principal elements of the cGAS-STING signaling cascade, summarizing recent research highlighting how cGAS-STING activation contributes to the pathogenesis of neurological diseases, including various autoimmune, autoinflammatory, and neurodegenerative diseases. Next, we outline selective small-molecule modulators that function as cGAS-STING inhibitors and summarize their mechanisms for treating multiple neurological diseases. Finally, we discuss key limitations of the current therapeutic paradigm and generate possible strategies to overcome them.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"105 ","pages":"Article 102691"},"PeriodicalIF":12.5,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143422741","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":"Bridging gap in the treatment of Alzheimer’s disease via postbiotics: Current practices and future prospects","authors":"Bushra Bashir ,&nbsp;Monica Gulati ,&nbsp;Sukriti Vishwas ,&nbsp;Gaurav Gupta ,&nbsp;Muralikrishnan Dhanasekaran ,&nbsp;Keshav Raj Paudel ,&nbsp;Dinesh Kumar Chellappan ,&nbsp;Krishnan Anand ,&nbsp;Poonam Negi ,&nbsp;Pankaj Kumar Singh ,&nbsp;Amarjitsing Rajput ,&nbsp;Kamal Dua ,&nbsp;Sachin Kumar Singh","doi":"10.1016/j.arr.2025.102689","DOIUrl":"10.1016/j.arr.2025.102689","url":null,"abstract":"<div><div>Aging is an extremely significant risk associated with neurodegeneration. The most prevalent neurodegenerative disorders (NDs), such as Alzheimer's disease (AD) are distinguished by the prevalence of proteinopathy, aberrant glial cell activation, oxidative stress, neuroinflammation, defective autophagy, cellular senescence, mitochondrial dysfunction, epigenetic changes, neurogenesis suppression, increased blood-brain barrier permeability, and intestinal dysbiosis that is excessive for the patient's age. Substantial body studies have documented a close relationship between gut microbiota and AD, and restoring a healthy gut microbiota may reduce or even ameliorate AD symptoms and progression. Thus, control of the microbiota in the gut has become an innovative model for clinical management of AD, and rising emphasis is focused on finding new techniques for preventing and/or managing the disease. The etiopathogenesis of gut microbiota in driving AD progression and supplementing postbiotics as a preventive and therapeutic treatment for AD is discussed. The review additionally discusses the use of postbiotics in AD prophylaxis and therapy, portraying them as substances that address senescence-triggered dysfunctions and are worthy of translating from bench to biopharmaceutical market in response to \"silver consumers\" needs. The current review examines and evaluates the impact of postbiotics as whole and specific metabolites, such as short-chain fatty acids (SCFAs), lactate, polyamines, polyphenols, tryptophan metabolites, exopolysaccharides, and bacterial extracellular vesicles, on the aging-associated processes that reinforce AD. Moreover, it provides an overview of the most recent data from both clinical and preclinical research involving the use of postbiotics in AD.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"105 ","pages":"Article 102689"},"PeriodicalIF":12.5,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143426873","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":"Binary and weighted network analysis and its applications to functional connectivity in subjective memory complaints: A resting-state fMRI approach","authors":"Sobhan Khodadadi Arpanahi,&nbsp;Shahrbanoo Hamidpour,&nbsp;Khatereh Ghasvarian Jahromi","doi":"10.1016/j.arr.2025.102688","DOIUrl":"10.1016/j.arr.2025.102688","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Introduction&lt;/h3&gt;&lt;div&gt;Despite normal cognitive abilities, subjective memory complaints (SMC) are common in older adults and are linked to mild memory impairment. SMC may be a sign of subtle cognitive decline and underlying pathological changes, according to research; however, there is not enough data to support the use of resting-state functional connectivity to identify early changes in the brain network before cognitive symptoms manifest.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Materials and methods&lt;/h3&gt;&lt;div&gt;In this study, the topological structure and regional connectivity of the brain functional network in SMC individuals were analyzed using graph theoretical analysis in both weighted and binarized network models, alongside healthy controls. Resting-state functional magnetic resonance imaging data was collected from 24 SMCs and 39 cognitively normal people. Analysis of both binary and weighted graph theory was done using the Dosenbach Atlas as a basis based on area under curves (AUCs) for the graph network parameters, which comprised of six node metrics and nine global measures. We then performed group comparisons using statistical analyses based on Network-Based Statistics functional connectomes. Finally, the relationship between global graph measures and cognition was examined using neuropsychological tests such as the Mini-Mental State Examination (MMSE) and the Alzheimer Disease Assessment Scale (ADAS score).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;The topologic properties of brain functional connectomes at both global and nodal levels were tested. The SMC patients showed increased functional connectivity in clustering coefficient global (P &lt; 0.00001), global efficiency (P &lt; 0.00001), and normalized characteristic path length or Lambda (P &lt; 0.00001), while there was decreased functional connectivity in Modularity (P &lt; 0.04542), characteristic path length (0.00001), and small-worldness or Sigma (P &lt; 0.00001) in binary networks model. In contrast, SMC patients only exhibited decreased functional connectivity in Assortativity identified by weighted networks model. Furthermore, some brain regions located in the default mode network, sensorimotor, occipital, and cingulo-opercular network in SMC patients showed altered nodal centralities. No significant correlation was found between global metrics and MMSE scores in both groups using binary metrics. However, in cognitively normal individuals, negative correlation was observed with weighted metrics in global and local efficiency and Lambda. While In SMC patients, a significant positive correlation was found between ADAS scores and local efficiency in both binary and weighted metrics.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;The findings suggest that functional impairments in SMC patients might be associated with disruptions in the global and regional topological organization of the brain's functional connectome, offering new and significant insights into the pathophysiological mechanisms underly","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"106 ","pages":"Article 102688"},"PeriodicalIF":12.5,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143416536","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":"News from the old: Aging features in the intracardiac, musculoskeletal, and enteric nervous systems","authors":"Severin Haider ,&nbsp;Eliza Sassu ,&nbsp;Dragana Stefanovska ,&nbsp;Mathew R. Stoyek ,&nbsp;Sebastian Preissl ,&nbsp;Luis Hortells","doi":"10.1016/j.arr.2025.102690","DOIUrl":"10.1016/j.arr.2025.102690","url":null,"abstract":"<div><div>Aging strongly affects the peripheral nervous system (PNS), triggering alterations that vary depending on the innervated tissue. The most frequent alteration in peripheral nerve aging is reduced nerve fiber and glial density which can lead to abnormal nerve functionality. Interestingly, the activation of a destructive phenotype takes place in macrophages across the PNS while a reduced number of neuronal bodies is a unique feature of some enteric ganglia. Single cell/nucleus RNA-sequencing has unveiled a striking complexity of cell populations in the peripheral nerves, and these refined cell type annotations could facilitate a better understanding of PNS aging. While the effects of senescence on individual PNS cell types requires further characterization, the use of senolytics appears to improve general PNS function in models of aging. Here, we review the current understanding of age-related changes of the intracardiac, musculoskeletal, and enteric nervous system sub-sections of the PNS, highlighting their commonalities and differences.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"105 ","pages":"Article 102690"},"PeriodicalIF":12.5,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143416541","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":"Neurobiological role and therapeutic potential of exercise-induced irisin in Alzheimer's disease management","authors":"Nandini Ratne ,&nbsp;Sakshi Jari ,&nbsp;Manasi Tadas ,&nbsp;Raj Katariya ,&nbsp;Mayur Kale ,&nbsp;Nandkishor Kotagale ,&nbsp;Dilip Madia ,&nbsp;Milind Umekar ,&nbsp;Brijesh Taksande","doi":"10.1016/j.arr.2025.102687","DOIUrl":"10.1016/j.arr.2025.102687","url":null,"abstract":"<div><div>Alzheimer's disease (AD) poses a significant obstacle in today's healthcare landscape, with limited effective treatments. Recent studies have revealed encouraging findings about how exercise-triggered irisin might help slow down the advancement of AD. Irisin, a myokine, released during physical activity, has garnered significant attention for its pleiotropic effects, extending beyond its traditional role in metabolic regulation. This review explores irisin's multifaceted potential in combating AD. Research indicates that irisin enhances synaptic plasticity, crucial for learning and memory, and exhibits neuroprotective properties that may slow AD progression by safeguarding neurons from degeneration. Additionally, irisin's ability to modulate inflammatory responses is significant, as neuroinflammation is a key feature of AD pathology. Irisin may also influence the metabolism and clearance of amyloid-beta plaques and tau tangles, hallmark pathological markers of AD. Furthermore, irisin boosts brain-derived neurotrophic factor expression, vital for neuronal health, and improves insulin glucose regulation, addressing impaired brain insulin signaling observed in AD. Exercise-induced irisin presents a non-pharmacological strategy, leveraging physical activity’s brain health benefits. Future research should focus on elucidating irisin’s mechanisms and conducting clinical trials to assess its therapeutic efficacy and safety in AD patients. Overall, irisin therapy offers a promising avenue for AD treatment, potentially slowing disease progression and enhancing cognitive function, paving the way for innovative therapeutic strategies in the fight against AD.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"105 ","pages":"Article 102687"},"PeriodicalIF":12.5,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143412077","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":"Senescence as a molecular target in skin aging and disease","authors":"Henriette Thau ,&nbsp;Bastian P. Gerjol ,&nbsp;Katharina Hahn ,&nbsp;Rosalie Wolff von Gudenberg ,&nbsp;Leonard Knoedler ,&nbsp;Kenneth Stallcup ,&nbsp;Maximilian Y. Emmert ,&nbsp;Timo Buhl ,&nbsp;Saranya P. Wyles ,&nbsp;Tamar Tchkonia ,&nbsp;Stefan G. Tullius ,&nbsp;Jasper Iske","doi":"10.1016/j.arr.2025.102686","DOIUrl":"10.1016/j.arr.2025.102686","url":null,"abstract":"<div><div>Skin aging represents a multifactorial process influenced by both intrinsic and extrinsic factors, collectively known as the skin exposome. Cellular senescence, characterized by stable cell cycle arrest and secretion of pro-inflammatory molecules, has been implicated as a key driver of physiological and pathological skin aging. Increasing evidence points towards the role of senescence in a variety of dermatological diseases, where the accumulation of senescent cells in the epidermis and dermis exacerbates disease progression. Emerging therapeutic strategies such as senolytics and senomorphics offer promising avenues to target senescent cells and mitigate their deleterious effects, providing potential treatments for both skin aging and senescence-associated skin diseases. This review explores the molecular mechanisms of cellular senescence and its role in promoting age-related skin changes and pathologies, while compiling the observed effects of senotherapeutics in the skin and discussing the translational relevance.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"105 ","pages":"Article 102686"},"PeriodicalIF":12.5,"publicationDate":"2025-02-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143392670","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":"Understanding of Alzheimer's disease pathophysiology for therapeutic implications of natural products as neuroprotective agents","authors":"Sneh Prabha,&nbsp;Arunabh Choudhury,&nbsp;Asimul Islam,&nbsp;Sonu Chand Thakur,&nbsp;Md. Imtaiyaz Hassan","doi":"10.1016/j.arr.2025.102680","DOIUrl":"10.1016/j.arr.2025.102680","url":null,"abstract":"<div><div>Alzheimer’s disease (AD) is a leading cause of dementia, affecting more than 24.3 million people worldwide in 2024. Sporadic AD (SAD) is more common and occurs in the geriatric population, while familial AD (FAD) is rare and appears before the age of 65 years. Due to progressive cholinergic neuronal loss and modulation in the PKC/MAPK pathway, β-secretase gets upregulated, leading to Aβ aggregation, which further activates tau kinases that form neurofibrillary tangles (NFT). Simultaneously, antioxidant enzymes are also upregulated, increasing oxidative stress (OS) and reactive species by impairing mitochondrial function, leading to DNA damage and cell death. This review discusses the classifications and components of several natural products (NPs) that target these signaling pathways for AD treatment. NPs, including alkaloids, polyphenols, flavonoids, polysaccharides, steroids, fatty acids, tannins, and polypeptides derived from plants, microbes, marine animals, venoms, insects, and mushrooms, are explored in detail. A synergistic combination of plant metabolites, together with prebiotics and probiotics has been shown to decrease Aβ aggregates by increasing the production of bioactive compounds. Toxins derived from venomous organisms have demonstrated effectiveness in modulating signaling pathways and reducing OS. Marine metabolites have also shown neuroprotective and anti-inflammatory properties. The cholera toxin B subunit and an Aβ₁₅ fragment have been combined to create a possible oral AD vaccine, that showed enhancement of cognitive function in mice. Insect tea is also a reliable source of antioxidants. A functional edible mushroom snack bar showed an increment in cognitive markers. Future directions and therapeutic approaches for the treatment of AD can be improved by focusing more on NPs derived from these sources.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"105 ","pages":"Article 102680"},"PeriodicalIF":12.5,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143375116","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}