International review of neurobiology最新文献

{"title":"Neurofilament light chain (NfL) as a biomarker for neurodegeneration: Protein biology, detection methods, and clinical applications.","authors":"Niranjana Rajesh, Jasmine R, Ryona Joji, Sowmya Sivakumar, Dileep Francis","doi":"10.1016/bs.irn.2026.05.009","DOIUrl":"https://doi.org/10.1016/bs.irn.2026.05.009","url":null,"abstract":"<p><p>Neurofilaments are vital structural components of neurons and play a central role in preserving axonal architecture and function. Among these, neurofilament light chain (NfL) has emerged as a sensitive biomarker of neuroaxonal injury. This chapter delineates the molecular organisation of neurofilaments, tracing their hierarchical assembly from coiled-coil dimers to mature filaments, and emphasises their contribution to axonal stability, calibre regulation, and intracellular transport. It further examines how perturbations in neurofilament homeostasis reflect neuronal damage across a broad spectrum of neurological disorders. Advances in analytical technologies, particularly ultrasensitive immunoassays such as Sioma and ELISA, have enabled robust quantification of NfL in cerebrospinal fluid and blood, facilitating its translation from experimental research into clinical practice. The diagnostic and prognostic relevance of NfL is examined across neurodegenerative, inflammatory, traumatic, and vascular diseases of the nervous system, with particular focus on Alzheimer's and Parkinson's diseases, highlighting its utility for disease monitoring and assessing treatment response. A discussion of clinical factors to consider when assessing NfL for disease diagnosis, along with its current challenges, is provided to draw attention to additional research. Through mechanistic insights spanning protein biology, clinical findings, and biomarker science, this chapter highlights NfL as a robust and non-invasive indicator of neuroaxonal injury applicable across distinct aetiologies. It posits that the systematic incorporation of NfL measurements into clinical workflows may refine nosological classification, enhance diagnostic and prognostic precision, and improve risk stratification at both individual and cohort levels, whilst informing evidence-based therapeutic decision-making and longitudinal patient management across a wide spectrum of neurological conditions.</p>","PeriodicalId":94058,"journal":{"name":"International review of neurobiology","volume":"191 ","pages":"447-485"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149042925","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Silent clues in blood: Proteomic approach for Alzheimer's disease.","authors":"Adriele Rebeca Vieira da Silva, Renata Santos Vieira da Conceição, Carla Mariana da Silva Medeiros, Michely da Silva Sousa, Jemmyson Romário de Jesus, Cícero Alves Lopes Júnior","doi":"10.1016/bs.irn.2026.08.009","DOIUrl":"https://doi.org/10.1016/bs.irn.2026.08.009","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by a prolonged prodromal phase, during which molecular alterations accumulate before the onset of cognitive symptoms. The development of minimally invasive biomarkers for early detection remains a major challenge in clinical diagnosis and therapeutic trials. Blood biomarkers have emerged as a promising alternative to cerebrospinal fluid (CSF) analysis and neuroimaging, although their implementation is limited by the low abundance of brain-derived proteins and the wide dynamic range of the blood proteome. Recent advances in proteomics technologies, including high-resolution liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS), immunoprecipitation coupled with mass spectrometry (IP-MS), and ultra-sensitive digital immunoassays, such as the single molecular array (Simoa), have enabled the quantification of protein biomarkers at sub-picogram concentrations. Currently, proteomic approaches have been combined with computational tools, such as artificial intelligence and machine learning, to increase the reliability in detecting differentially abundant blood proteins associated with the preclinical stages of Alzheimer's disease (AD). In this chapter, we discuss the current state of plasma proteomics in Alzheimer's disease, with a focus on biomarker proteins, analytical methodologies, and translational challenges for the clinical application of blood-based protocols. In fact, research focused on blood protein biomarkers may reveal key clues for fully understanding the etiology of AD, enabling earlier diagnosis and monitoring of its progression, thereby paving the way for research targeting a cure.</p>","PeriodicalId":94058,"journal":{"name":"International review of neurobiology","volume":"191 ","pages":"345-402"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149043080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intestinal microbiota in neurodegeneration and ageing: Mechanisms, pathways, and therapeutic interventions.","authors":"Gopal Khodve, Shaswat Raval, Sugato Banerjee","doi":"10.1016/bs.irn.2026.05.015","DOIUrl":"https://doi.org/10.1016/bs.irn.2026.05.015","url":null,"abstract":"<p><p>The human gut microbiota represents a complex ecosystem of trillions of microorganisms with profound implications for neurological health. Emerging evidence demonstrates that dysbiosis, an imbalance in microbial composition and function, plays a crucial role in the pathogenesis of neurodegenerative diseases and age-related cognitive decline. This chapter summarizes current knowledge of the microbiota-gut-brain axis (MGBA) and elucidates how intestinal microbes and their metabolites communicate with the central nervous system via neural, immune, endocrine, and metabolic pathways. We examine the mechanistic links between gut dysbiosis and specific neurodegenerative conditions, including Alzheimer's disease (AD), Parkinson's disease (PD), Amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), and Multiple sclerosis (MS). Furthermore, we explore age-related changes in the microbiota and their contributions to neuroinflammation, immunosenescence, and cognitive decline. Finally, we evaluate therapeutic interventions targeting the microbiota, including probiotics, prebiotics, synbiotics, and dietary modulation as promising strategies to prevent and ameliorate neurodegenerative pathology. The chapter provides a comprehensive summary of how microbiota-targeted approaches may delay ageing and neurodegeneration.</p>","PeriodicalId":94058,"journal":{"name":"International review of neurobiology","volume":"188 ","pages":"199-229"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148698711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic dysregulation in Alzheimer's disease: Mechanisms, markers, and therapeutic prospects.","authors":"Radhika Mittal, Priya, Jyotirmoy Banerjee, Aparna Dixit","doi":"10.1016/bs.irn.2026.05.011","DOIUrl":"https://doi.org/10.1016/bs.irn.2026.05.011","url":null,"abstract":"<p><p>Metabolic dysregulation has emerged as a crucial pathogenic factor that contributes in progression of Alzheimer's disease (AD), and is often found to precede classical AD's pathologies, the amyloid-β accumulation and hyperphosphorylated tau proteinopathies. The key metabolic underpinnings associated with Alzheimer's disease (AD) includes cerebral glucose hypometabolism, insulin resistance, mitochondrial dysfunction, altered lipid metabolism, vascular and systemic metabolic impairments, disrupted amino acid and nitrogen metabolism driving secondary metabolic disturbances. The chapter outlines the current evidences on dysregulated metabolic processes, and highlights emerging metabolic biomarkers that are identified through advanced neuroimaging modalities, plasma/cerebrospinal fluid (CSF) profiles, lipidomic signatures and markers of mitochondrial impairment, underscoring their diagnostic and prognostic potential. Furthermore, the chapter discusses about the therapeutic prospects targeting metabolic pathways, addressing current challenges in development of therapeutic strategies, reinforcing the need for integrative and precision-based interventions for early diagnosis and disease modifying therapeutic strategies in AD.</p>","PeriodicalId":94058,"journal":{"name":"International review of neurobiology","volume":"188 ","pages":"397-434"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148703025","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Starved synapses: Gut microbiome dysbiosis and its role in Alzheimer's glucose impairment.","authors":"Riddhi Upadhyay, Sneha Santhosh, R Malathi, P Saravana Kumari, S Vijayanand, Murugan Sevanan","doi":"10.1016/bs.irn.2026.01.010","DOIUrl":"10.1016/bs.irn.2026.01.010","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is increasingly recognised as a multifactorial disorder driven by metabolic, microbial, and neuroinflammatory imbalances. The study of the research results proposes that gut dysbiosis and impaired brain glucose metabolism are closely interrelated through the gut-brain metabolism axis. Changes in the intestinal microbiome may disrupt insulin sensitivity, cause systemic inflammation, and disrupt the blood-brain barrier, worsening neuronal glucose deficits and facilitating amyloid-β (Aβ) aggregation and tau phosphorylation. Alongside, neurodegenerative cascades are further enhanced by neuronal metabolic reprogramming, characterised by decreased glucose uptake, dysfunctional glycolytic enzymes, and oxidative stress. Short-chain fatty acids (SCFAs) are mainly butyrate, which have a neuroprotective effect in regulating inflammation and gut integrity, and dysbiosis causes increased pro-inflammatory cytokines and endotoxin leakage. This two-way communication network provides new therapeutic opportunities, such as probiotics, prebiotics, nutritional control, and metabolic reprogramming interventions, to regain homeostasis and prevent the advancement of AD.</p>","PeriodicalId":94058,"journal":{"name":"International review of neurobiology","volume":"186 ","pages":"241-264"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148229857","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From metals to mitochondria: Linking trace elements to energy crisis in Alzheimer's disease.","authors":"Carla Mariana da Silva Medeiros, Renata Santos Vieira da Conceição, Mikael Kélvin de Albuquerque Mendes, Jemmyson Romário de Jesus, Cícero Alves Lopes Júnior","doi":"10.1016/bs.irn.2026.05.003","DOIUrl":"10.1016/bs.irn.2026.05.003","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a chronic, progressive neurodegenerative disorder and the most common cause of dementia, with a high incidence in the global population, especially in the elderly. AD presents a complex pathogenesis including protein misfolding and aggregation, neuroinflammation, oxidative stress, mitochondrial dysfunction, and on. Currently, the imbalance of essential metals has been associated with AD pathology. Although trace elements such as iron (Fe), zinc (Zn), copper (Cu), and manganese (Mn) are vital for physiological processes in the brain, their dyshomeostasis, whether due to deficiency or excess, mainly impairs energy metabolism by increasing the production of free radicals (e.g., ROS), resulting in oxidative stress and, subsequent mitochondrial dysfunction. Excess metals impair the tricarboxylic acid (TCA) cycle and electron transport chain (ETC) in mitochondria. Thus, metal ions are closely linked to the mitochondrial energy-transducing capacity and redox homeostasis. The brain is highly susceptible and sensitive to metal-mediated metabolic crisis, leading to neuronal dysfunction, a key factor in the progression and severity of AD. Traditional treatments for AD pathology are based on acetylcholinesterase inhibitors and anti-amyloid approaches, but metal chelation has shown potential in reversing the clinical condition of the disease. Herein, we discuss the contribution of metal imbalance to the metabolic energy impairment of the brain in AD, highlighting its relationship with mitochondrial dysfunction. Some therapeutic approaches involving restoration of metal ion homeostasis are discussed.</p>","PeriodicalId":94058,"journal":{"name":"International review of neurobiology","volume":"186 ","pages":"265-315"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148229846","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insulin resistance and obesity: Drivers of energy crisis for Alzheimer's disease.","authors":"Pooja Singh, Bhupesh Vaidya, Pallavi Upadhayay, Shyam Sunder Sharma, Ashok Kumar Datusalia","doi":"10.1016/bs.irn.2026.05.018","DOIUrl":"10.1016/bs.irn.2026.05.018","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is increasingly recognized as a disorder driven not only by classical neuropathological hallmarks but also by profound disturbances in brain energy metabolism. Growing evidence points to insulin resistance and obesity as major contributors to this metabolic crisis, linking peripheral metabolic dysfunction to central neurodegenerative processes. This chapter explores AD in the light of bioenergetic failure, highlighting the epidemiological and mechanistic connections between impaired insulin signaling, excess adiposity, and cognitive decline. The chapter further highlights how obesity-related inflammation, adipokine imbalance, and gut-brain axis dysregulation accelerates central insulin resistance and neuronal vulnerability. Evidence for glucose hypometabolism, mitochondrial failure, and disrupted astrocyte-neuron metabolic coupling in AD is reviewed, positioning amyloid and tau pathology as downstream consequences of sustained energy insufficiency. Finally, emerging therapeutic strategies aimed at restoring metabolic balance ranging from insulin-based interventions to lifestyle and mitochondria-targeted approaches are discussed, underscoring the potential of metabolic restoration as a disease-modifying strategy in Alzheimer's disease.</p>","PeriodicalId":94058,"journal":{"name":"International review of neurobiology","volume":"187 ","pages":"39-90"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148440389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic reprogramming in Alzheimer's disease: Interaction between receptor tyrosine kinase signaling, noncoding RNAs, and Neuron-Glia energy networks.","authors":"Ankita Karmakar, Puja Roycowdhury, Priyanka Sengupta, Debashis Mukhopadhyay","doi":"10.1016/bs.irn.2026.02.007","DOIUrl":"10.1016/bs.irn.2026.02.007","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is increasingly understood as a disorder involving impaired brain energy metabolism rather than being solely caused by amyloid and tau pathology. This chapter offers a comprehensive overview of how glucose hypometabolism, mitochondrial dysfunction, and disrupted neuron-astrocyte metabolic coupling collectively creates an \"energy crisis\" in vulnerable neuronal circuits. Early issues with glucose transport (GLUT1/3/4), reduced glycolytic flux, TCA cycle problems, and excessive mitochondrial fission all contribute to decreased ATP production and increased oxidative stress. Along with these metabolic disturbances, receptor tyrosine kinase (RTK) pathways-including insulin/IGF-1, TrkB/BDNF, FGFRs, and EGFR-lose their regulatory control, leading to insulin resistance, synaptic failure, and increased vulnerability to Aβ and tau toxicity. The chapter also highlights noncoding RNAs (miRNAs and lncRNAs) as key post-transcriptional regulators of metabolic and RTK signaling networks. Harmful miRNAs (such as miR-34a, miR-210-3p) suppress glycolytic enzymes and mitochondrial genes, while protective miRNAs (miR-23a/b, miR-455-3p, miR-195) decrease in AD. Metabolic lncRNAs, like EPB41L4A-AS1, decline with age and contribute to NAD⁺ depletion and bioenergetic imbalance. Recognizing the link between RTK dysregulation and ncRNA-driven metabolic control reveals new therapeutic possibilities to restore mitochondrial function, enhance neurotrophic support, and re-establish energy balance in the AD brain.</p>","PeriodicalId":94058,"journal":{"name":"International review of neurobiology","volume":"187 ","pages":"281-330"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148440393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bioenergetic impairment-induced Tau acetylation: Converging pathways in Alzheimer's disease.","authors":"Basavaraju K C, Poornima Priyadarshini","doi":"10.1016/bs.irn.2026.05.020","DOIUrl":"10.1016/bs.irn.2026.05.020","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is increasingly recognized as a metabolic disorder in which disruptions in cellular energy metabolism play a central role in its progression. The dysregulated metabolism of carbohydrates, proteins, fatty acids, and nucleic acids collectively impairs neuronal bioenergetics, leading to mitochondrial dysfunction and reduced ATP production. This impaired energy metabolism trigger a cascade of cellular stress responses, including endoplasmic reticulum (ER) stress, oxidative and inflammatory responses, and increased generation of amyloid-β (Aβ), thereby exacerbating neuronal vulnerability. A critical downstream consequence of bioenergetic failure is the altered epigenetic and post-translational regulatory enzymes, particularly the acetyltransferase EP300 and the NAD⁺-dependent deacetylases known as sirtuins. An imbalance in the activity of these enzymes promotes the abnormal tau acetylation, which disrupts tau-microtubule interactions and promotes tau aggregation, ultimately accelerating neurodegeneration. Emerging evidence suggests tau acetylation as a mechanistic link between metabolic dysfunction and hallmark pathological characteristics of AD, suggesting bioenergetic impairment directly regulate tau pathology. Thus, understanding the metabolic pathways that drive tau acetylation may offer new therapeutic targets aimed at restoring neuronal energy balance, re-establishing acetylation homeostasis, and potentially slowing the progression of AD.</p>","PeriodicalId":94058,"journal":{"name":"International review of neurobiology","volume":"187 ","pages":"17-38"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148440400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of ESCRT pathway and autophagy in neurodegenerative diseases.","authors":"Shweta Dongre, Naveen Soni, Bhawana Bissa","doi":"10.1016/bs.irn.2026.05.022","DOIUrl":"https://doi.org/10.1016/bs.irn.2026.05.022","url":null,"abstract":"<p><p>Neurodegenerative diseases are characterized by progressive neuronal dysfunction and loss resulting from impaired proteostasis and vesicular trafficking. Neurons are particularly vulnerable to these processes due to their post-mitotic nature and complex architecture. Autophagy and the endolysosomal system constitute the primary degradative pathways responsible for maintaining neuronal homeostasis. However, increasing evidence indicates that their effective function critically depends on coordination with the endosomal sorting complexes required for transport (ESCRT). Beyond their canonical role in multivesicular body biogenesis and membrane scission, ESCRT components are now recognized as essential regulators of autophagosome closure, amphisome formation, autophagosome-lysosome fusion, and endolysosomal membrane repair. Disruption of this ESCRT-autophagy interface has emerged as a common pathological feature across major neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis/frontotemporal dementia. This review synthesizes evidence from genetic, biochemical, and neuropathological studies to highlight shared molecular nodes, such as ESCRT-III components, the VPS4 ATPase, the adaptor protein ALIX, and late endosomal regulators, including Rab7, that couple membrane remodeling to autophagic flux. Failure of these regulatory checkpoints destabilizes endolysosomal integrity, arrests autophagic maturation, and promotes the accumulation of toxic protein species, thereby driving progressive neuronal degeneration. By framing neurodegeneration through the lens of ESCRT-autophagy coupling failure, this review provides a unified mechanistic perspective that links diverse pathogenic proteins to shared cellular vulnerabilities and identifies ESCRT-mediated membrane dynamics as a critical determinant of neuronal survival.</p>","PeriodicalId":94058,"journal":{"name":"International review of neurobiology","volume":"187 ","pages":"1-16"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148440410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}