International review of neurobiology最新文献

{"title":"Running out the clock: Circadian rhythm dysfunction in cognitive disease.","authors":"Kenneth Maiese","doi":"10.1016/bs.irn.2026.08.015","DOIUrl":"10.1016/bs.irn.2026.08.015","url":null,"abstract":"<p><p>Lifespan is increasing such that within a few decades approximately twenty percent of the world's population is expected to be greater than sixty years of age. In concert with global aging of the population, neurodegenerative disorders have become the leading cause of disability with dementia now the seventh leading cause of death worldwide. Despite multi-faceted treatment approaches for disorders of cognition that include Alzheimer's disease and multiple sclerosis, present therapies ultimately cannot halt disease progression and eventually cognitive impairment continues unabated. Furthermore, co-morbidities, such as metabolic disorders with diabetes mellitus, also lack strategies to prevent disease progression. Given these clinical challenges for cognitive loss, innovative avenues of investigation that involve mammalian chronobiology with circadian rhythm clock genes and related pathways of aging, cellular senescence, oxidative stress, metabolic dysfunction, sleep fragmentation, apolipoprotein E, programmed cell death, silent mating type information regulation 2 homolog 1 (Saccharomyces cerevisiae), nicotinamide adenine dinucleotide, the gut microbiota, and glucagon-like peptide-1 receptor agonism may offer exceptional promise for forging new strategies for cognitive disease treatment. These pathways are intimately linked to circadian rhythm processes, are complex in generating biological outcomes, can broadly influence clinical translation of both short- and long-term considerations for cognitive disease care, and necessitate dissection of their precise regulatory mechanisms with the benefit from early diagnostic platforms as well as artificial intelligence and machine learning applications to foster translation of these pathways into effective clinical treatments.</p>","PeriodicalId":94058,"journal":{"name":"International review of neurobiology","volume":"190 ","pages":"231-306"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13595999/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149019171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advances in nanomaterial-based biomarker detection for neurodegenerative diseases: Special focus on Alzheimer's and Parkinson's disease.","authors":"Shajahan Azeez, Raj Kumar Chinnadurai, Saravanaraman Ponne, Durairaj Duraikannu","doi":"10.1016/bs.irn.2026.07.004","DOIUrl":"https://doi.org/10.1016/bs.irn.2026.07.004","url":null,"abstract":"<p><p>Amyloid-β aggregation, tau hyperphosphorylation, and α-synuclein misfolding are pathological processes that occur decades before clinical onset in neurodegenerative diseases like Alzheimer's disease (AD) and Parkinson's disease (PD), but detection is still symptom based and technologically insufficient. Disease staging has been redefined by biomarker-centric frameworks, especially the AT(N) classification. However, low abundance, structurally heterogeneous biomarkers in complex biofluids are not resolved by current detection strategies because of limited sensitivity, matrix interference, and lack of conformational specificity. In this regard, nanomaterial enabled sensing platforms offer unique physicochemical properties: magnetic nanostructures enable background independent detection, carbon nanomaterials enable electrochemical signal amplification through improved charge transfer, and plasmonic nanostructures enable label-free optical detection via surface plasmon resonance. When combined, these systems allow for real-time analysis in physiologically relevant matrices, multiplexed detection, and femtomolar sensitivity. Despite advancements in analytical techniques, the practical application of these technologies is hindered by challenges such as biofouling, inconsistencies between batches, and a lack of adequate clinical validation. This review examines the potential of nanomaterial-based sensing strategies for developing clinically relevant neurodiagnostics, categorizes them systematically, and links them to biomarker profiles for AD and PD.</p>","PeriodicalId":94058,"journal":{"name":"International review of neurobiology","volume":"191 ","pages":"175-224"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149042696","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":"A comprehensive review on therapeutics and diagnostic agents targeting acetyl and butyryl cholinesterases for AD.","authors":"Vishal Chaurasia, Sanjib Das Modak, Gireesh Kumar Singh, Gyan Modi","doi":"10.1016/bs.irn.2026.05.017","DOIUrl":"https://doi.org/10.1016/bs.irn.2026.05.017","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a progressive, irreversible, and multifaceted neurodegenerative disorder characterized by cognitive decline, memory loss, and behavioral impairment, posing a major global health challenge. Its multifactorial pathology includes cholinergic dysfunction, amyloid-β deposition, tau hyperphosphorylation, oxidative stress, and neuroinflammation. Among these, impairment of the cholinergic system, characterized by reduced acetylcholine levels, plays a crucial role in cognitive deficits. The enzymes acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), which hydrolyze acetylcholine, are closely involved in disease progression and serve as important therapeutic and diagnostic targets in AD. This book chapter provides a comprehensive overview of therapeutic and diagnostic agents targeting AChE and BChE in AD, and discusses small-molecule inhibitors, multifunctional ligands, and emerging strategies to modulate cholinesterase activity and restore cholinergic neurotransmission, alleviating disease symptoms. In addition, the chapter highlights advances in diagnostic approaches using fluorescent probes, particularly near-infrared (NIR) probes, for selective detection and imaging of AChE and BChE, including their molecular design, photophysical properties, enzyme selectivity, and mechanisms of action, all of which are critically examined. Targeting AChE and BChE offers a dual advantage in AD by enabling both symptomatic treatment and early-stage diagnosis. This chapter aims to present a clear and comprehensive overview of recent advances in therapeutic and diagnostic approaches, offering meaningful insights for researchers in developing effective strategies for the treatment and monitoring of AD.</p>","PeriodicalId":94058,"journal":{"name":"International review of neurobiology","volume":"188 ","pages":"145-198"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148703012","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":"The potential of HDAC inhibitors for Alzheimer's disease.","authors":"Vedika Jain, Sharda Bharti","doi":"10.1016/bs.irn.2026.01.005","DOIUrl":"https://doi.org/10.1016/bs.irn.2026.01.005","url":null,"abstract":"<p><p>Alzheimer's disease is a progressive neurodegenerative condition characterized by cognitive deterioration, memory loss, and persistent neuroinflammation. Notwithstanding considerable scientific advancements, current therapy strategies predominantly address symptoms and are ineffective in arresting illness progression. Recent studies have demonstrated the crucial role of epigenetic changes, especially histone modifications, in the pathophysiology of Alzheimer's disease. Removal of the acetyl group from histones and non-histone proteins by histone deacetylases (HDACs) plays a pivotal role in the regulation of gene expression, synaptic plasticity, and neuronal survival. Such changes lead to dysregulated HDAC activity, which is further associated with significant clinical characteristics of Alzheimer's disease, including amyloid-beta accumulation, tau hyperphosphorylation, oxidative stress, and neuroinflammation. In Alzheimer's disease and other neurodegenerative diseases, the histone acetylation equilibrium is markedly disrupted, resulting in a shift towards hypoacetylation, which further inhibits the production of neuroprotective genes. Pharmacological inhibition of HDACs can reinstate hyperacetylation, therefore facilitating neuroprotective effects. This chapter explores the therapeutic potential of HDAC inhibitors in relation to Alzheimer's disease. This chapter also focuses on various HDAC isoforms associated with disease progression and explores the detailed mechanism by which HDAC inhibitors affect the epigenetic regulation and neuronal function. Preclinical investigations focusing on the role of HDAC inhibitors in mitigating neuroinflammation and Alzheimer's diseases, with a special focus on HDAC inhibitors in clinical trials, present intriguing opportunities for therapeutic advancement. The chapter further explores various challenges such as off-target effects, restricted isoform specificity, and inadequate blood-brain barrier permeability. To address these constraints, various strategies such as isoform-selective inhibitors, targeted delivery methods, and combination treatments are also explored. Thus, the chapter provides in-depth information on the role of HDAC inhibitors, which hold significant potential as disease-modifying agents in the treatment of Alzheimer's disease.</p>","PeriodicalId":94058,"journal":{"name":"International review of neurobiology","volume":"188 ","pages":"273-298"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148703146","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":"Cannabinoids and therapeutic potential in neuropsychiatry.","authors":"D Dilara Ertenu, Apurva Papolu, Nyya Anderson, Elisheva Wecker, Aaron J Hauptman, Jay A Salpekar","doi":"10.1016/bs.irn.2026.08.030","DOIUrl":"https://doi.org/10.1016/bs.irn.2026.08.030","url":null,"abstract":"<p><p>Cannabinoids have therapeutic utility in some specific areas of medicine, including as an anti-nausea adjunct for chemotherapy and as an anti-inflammatory agent, among others. However, as a therapeutic agent in neuropsychiatric conditions, the data is more limited. Cannabis itself is viewed as a recreational drug of abuse with no medical utility; however, the reality may be more complex when considering individual components of the plant. Cannabinoid components may have some benefit as therapeutic agents in neuropsychiatry, with cannabidiol most often purported to be a therapeutic agent for some seizure disorders. However, recent studies suggest that the cannabis plant is proving to be broader and more complicated in how it delivers potential therapeutic effects. It may be that a combination of components is more effective than any one component. This chapter reviews the medical usage of cannabinoids in neuropsychiatric illness, as reported in the literature, and proposes future approaches that may more effectively avail the attributes of this plant.</p>","PeriodicalId":94058,"journal":{"name":"International review of neurobiology","volume":"190 ","pages":"127-160"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149019078","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 risk detection to brain health action: The CheckPD-CheckBRAIN pathway across the missing middle in Parkinson's disease.","authors":"Roongroj Bhidayasiri, Jirada Sringean, Saisamorn Phumphid, Chanawat Anan, Yoshikazu Ugawa, Christopher Chen, Grisada Boonrach, Claudio L A Bassetti","doi":"10.1016/bs.irn.2026.08.016","DOIUrl":"https://doi.org/10.1016/bs.irn.2026.08.016","url":null,"abstract":"<p><p>Brain health has entered an implementation era, yet practical pathways for translating risk detection into meaningful action remain underdeveloped, particularly in low- and middle-income settings. Parkinson's disease (PD) offers a useful tracer condition for this challenge because it is common, progressive, clinically recognisable, functionally disabling, and highly sensitive to health-system capacity across awareness, referral, diagnosis, treatment, rehabilitation, caregiver support, and longitudinal monitoring. This review uses Thailand's CheckPD™ programme as an applied anchor for examining how digital PD screening can move beyond case-finding toward broader brain health implementation. CheckPD provides a population-facing digital screening and risk-stratification layer for PD and prodromal signals, but screening alone is insufficient. Without interpretation, risk communication, triage, referral completion, prevention advice, rehabilitation linkage, and follow-up, earlier detection may create earlier labelling rather than earlier benefit. We define this transition zone as the \"missing middle.\" To address this gap, we propose CheckBRAIN™ as a post-screening brain health action framework organised around three domains: prevention pathways, resilience-building, and longitudinal brain health monitoring. Across primary prevention, CheckBRAIN promotes modifiable brain health and non-communicable disease risk reduction; across secondary prevention, it monitors risk trajectories, new prodromal symptoms, and conversion to clinical disease; and across tertiary prevention, it aims to preserve function, delay milestones, reduce complications, and support caregivers in established PD. By integrating prodromal PD risk science, digital screening, implementation science, resilience concepts, and global brain health strategy, the CheckPD-CheckBRAIN pathway offers a practical model for moving from early detection of neurodegeneration toward earlier, accessible, and actionable brain health care.</p>","PeriodicalId":94058,"journal":{"name":"International review of neurobiology","volume":"190 ","pages":"175-229"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149019038","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":"Vulnerability in the womb: Charting the effects of prenatal cannabinoid exposure to mitigate developmental actions on dopamine metabolic capacities and circuits.","authors":"Federico Brandalise, Erika Lorenzi, Miriam Melis","doi":"10.1016/bs.irn.2026.08.020","DOIUrl":"https://doi.org/10.1016/bs.irn.2026.08.020","url":null,"abstract":"<p><p>Prenatal cannabis exposure (PCE) is increasingly recognized as a major public health concern as cannabis use during pregnancy continues to rise worldwide. While early studies focused on cannabinoid receptor-mediated alterations in neurotransmission, emerging evidence indicates that PCE induces long-lasting developmental reprogramming affecting neural circuits, metabolism, and endocrine regulation. In this roadmap, we propose a shift from viewing PCE as a discrete synaptic disturbance to considering it a disorder of developmental coordination. We discuss how prenatal cannabinoid exposure may alter mesolimbic dopamine circuit maturation through the interaction of neuronal excitability, mitochondrial bioenergetics, and stress-related hormonal signaling. Particular attention is given to mitochondrial-circuit coupling in dopaminergic neurons and the potential role of mitochondrial cannabinoid receptors (mtCB1) in shaping long-term neuronal function. We further highlight the contribution of astrocytes, microglia, and neuroimmune processes in determining vulnerability or resilience trajectories. We propose that PCE generates latent neurobiological vulnerabilities that may emerge during adolescence or later life when challenged by environmental or physiological stressors. This framework provides new opportunities for early intervention, and prevention, while also offering insights into how early-life metabolic and mitochondrial dysfunction may contribute to lifelong brain vulnerability, including increased susceptibility to age-related neurodegenerative disorders such as Alzheimer's disease.</p>","PeriodicalId":94058,"journal":{"name":"International review of neurobiology","volume":"190 ","pages":"1-15"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149019266","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":"Blood-based biomarkers in Alzheimer's and Parkinson's disease: From molecular pathology to therapeutic potential.","authors":"Priya, Radhika Mittal, Jyotirmoy Banerjee, Aparna Dixit","doi":"10.1016/bs.irn.2026.02.006","DOIUrl":"https://doi.org/10.1016/bs.irn.2026.02.006","url":null,"abstract":"<p><p>Alzheimer's (AD) and Parkinson's disease (PD) represent a major class of neurodegenerative disorders characterized by different proteinopathies with amyloid-β plaques and tau tangles in AD, while α-synuclein containing Lewy bodies in PD, specific molecular signatures. Alongside this central mechanism, they share pathological cascades including axonal degeneration, synaptic dysfunction, glial activation and neuroinflammation. The emergence of blood-based biomarkers, represents a paradigm shift in the field of diagnosis and therapeutics by addressing these core pathological mechanism of central nervous system. This chapter highlights a overview of blood-based biomarkers emerging in the field of AD and PD, exploring the clinical utility of core pathology markers (Aβ42/40, p-tau species, and α-synuclein), alongside other neurodegenerative markers such as neurofilament light chain and glial activation markers like GFAP. Beyond the diagnosis, we emphasize on the potential role of blood-based biomarkers as a surrogate and pharmacodynamic endpoint in disease modifying clinical trial development, facilitating dose optimization and target engagement. Future prospects empathize on the use of multimodal approach integration, trajectory modeling and novel target discovery. Collectively, these blood-based biomarkers enable transition of neurodegenerative disorders treatment from symptom-based classification to towards a mechanism targeted therapeutic framework.</p>","PeriodicalId":94058,"journal":{"name":"International review of neurobiology","volume":"191 ","pages":"225-273"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149042764","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":"The emerging landscape of circulatory biomarkers in Alzheimer's disease.","authors":"Sakshi Kumari, Amaan Rais, Mohd Suhail Ashar, Abhinay Kumar Singh, Masroor Anwar, Rashmita Pradhan, Sharmistha Dey","doi":"10.1016/bs.irn.2026.08.008","DOIUrl":"https://doi.org/10.1016/bs.irn.2026.08.008","url":null,"abstract":"<p><p>Early detection of dementia remains a critical challenge for both researchers and clinicians. Blood-based biomarkers have emerged as a primary focus because they are less expensive and more scalable than neuroimaging or cerebrospinal fluid (CSF) analysis. Blood-based biomarkers offer a tool for screening, diagnosis, risk assessment, and therapeutic development. For clinical approval, biomarkers must be accessible, affordable, and minimally invasive. Inflammation, oxidative stress and mitochondrial dysfunction are the key events responsible for the initiation of formation of disease hallmarks, i.e., Aβ and pTau. This chapter explores the pathophysiology of Alzheimer's Disease (AD) to identify peripheral molecular markers associated with these early events and facilitate the development of combinatorial therapies. Shifting the focus from traditional cross-sectional neuroimaging towards cost-effective, longitudinal blood-based panels represents a vital step in managing the global burden of AD.</p>","PeriodicalId":94058,"journal":{"name":"International review of neurobiology","volume":"191 ","pages":"275-343"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149043058","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":"Glutamate-Glutamine metabolism and transport, implications in Parkinson's disease.","authors":"Ragini Raghu, Subashchandrabose Chinnathambi","doi":"10.1016/bs.irn.2026.01.001","DOIUrl":"10.1016/bs.irn.2026.01.001","url":null,"abstract":"<p><p>Parkinson's disease (PD) is a common neurodegenerative condition caused by the selective loss of dopaminergic neurons in the substantia nigra (SN) and the formation of Lewy bodies due to α-Synuclein (α-Syn) aggregation in the midbrain. Glutamate (Glu) is an excitatory neurotransmitter that plays an important role in the normal functioning of the basal ganglia circuit. It has been shown recently that Glu receptors are involved in the regulation of neurotransmitter release, neuron excitability and long-term plasticity and the altered mechanisms in Parkinson's disease. Glu is produced in the cytoplasm and is packed and stored in vesicles by vesicular glutamate transporters (VGLUTs). Following its release into the synaptic cleft, it exerts its physiological effects by binding to ligand-gated ion channels (ionotropic glutamate receptors (iGluRs)) and G-protein coupled receptors (metabotropic glutamate receptors (mGluRs)). Lack of glutamate reuptake or enzymatic decomposition results in Glu accumulation at the synapse, causing excitotoxicity. This is prevented by excitatory amino acid transporters (EAATs), which reabsorb the extracellular Glu. Furthermore, elevated extracellular glutamate levels prevent cystine uptake, which results in oxidative glutamate toxicity and glutathione depletion. Currently, there are no effective treatments for Parkinson's disease, as most of the drugs that exist have greater side effects, like dyskinesia. Hence, the identification of new potential drug targets is an important factor for improving the therapeutic strategies to combat the disease. Therefore, in this review, we aim to discuss about characteristics of these receptors and transporters and highlight the neuroprotective effects and pharmacological manifestations in Parkinson's disease.</p>","PeriodicalId":94058,"journal":{"name":"International review of neurobiology","volume":"186 ","pages":"75-106"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148229844","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}