International review of neurobiology最新文献

{"title":"Circadian rhythm, metabolic stress, and Alzheimer's disease.","authors":"Vaishali Saini, Siddharth Singh, Raunak Kumar, Md Shahadab, Hem Chandra Jha","doi":"10.1016/bs.irn.2026.05.004","DOIUrl":"10.1016/bs.irn.2026.05.004","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder. Beyond hereditary factors related to an individual's genetics, acquired traits are becoming increasingly common, including lifestyle changes such as diet and pathogenic infections. This brings about the involvement of metabolic stress and gut-brain axis dysfunction in the progression of AD. Recent studies have revealed that circadian rhythms not only regulate brain energy metabolism but also orchestrate changes in gut microbiota, inducing neurological modulations. Gut-derived metabolites and microbial signals can modulate host circadian gene expression, thereby influencing neuroinflammation. Metabolic stresses, characterized by impaired glucose utilization, mitochondrial dysfunction, and oxidative stress, exacerbate this cycle through systemic inflammation and gut dysbiosis. Additionally, dietary patterns and timing, such as time-restricted feeding, have been known to benefit both the circadian clock and gut-brain axes, thereby reducing neuroinflammation and improving cognitive outcomes. Therefore, this chapter synthesizes the emerging evidence on the interconnected roles of circadian rhythm, gut microbiota, and metabolic stresses in AD pathogenesis. It highlights the mechanistic insights into how chronobiology and nutrition can be leveraged to restore gut-brain metabolic homeostasis, offering innovative strategies for early intervention of Alzheimer's disease.</p>","PeriodicalId":94058,"journal":{"name":"International review of neurobiology","volume":"186 ","pages":"215-240"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148229849","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":"Liquid-liquid phase separation of tau in Alzheimer's disease.","authors":"Sangita Rajkhowa, Timir Tripathi","doi":"10.1016/bs.irn.2026.01.009","DOIUrl":"10.1016/bs.irn.2026.01.009","url":null,"abstract":"<p><p>Tau is a microtubule-associated protein that plays a central role in neuronal stability and axonal transport. However, under pathological conditions, it undergoes structural and functional changes that lead to Alzheimer's disease (AD) and related tauopathies. Recent evidence highlights liquid-liquid phase separation (LLPS) as a critical mechanism underlying tau aggregation and the subsequent formation of neurofibrillary tangles (NFTs). This chapter explores the properties of tau, including its intrinsically disordered nature, isoforms, and post-translational modifications (PTMs), that predispose it to LLPS. We discuss the thermodynamic and molecular principles of LLPS, with emphasis on the interplay between multivalent interactions, crowding effects, RNA binding, and cofactors that modulate the formation of tau condensates. Special attention is given to the transition from dynamic, reversible tau droplets to irreversible fibrillar assemblies. The chapter further examines how truncation and PTM cross-talk alter the phase behavior and aggregation propensity of tau. Cellular implications of tau LLPS, including its role in stress granules, synaptic dysfunction, and seeding of NFTs, are also analyzed. Finally, we highlight the regulatory roles of chaperones, metal ions, and interacting proteins and underscore the therapeutic potential of targeting tau phase separation. Together, this synthesis positions the LLPS of tau as a pivotal event in AD pathogenesis and a promising target for therapeutic intervention.</p>","PeriodicalId":94058,"journal":{"name":"International review of neurobiology","volume":"187 ","pages":"219-279"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148440405","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":"Light talks: The role of biophoton in cellular communication.","authors":"Jaimie Hoh Kam, Ifigeneia Kalampouka, Tigrane Cantat-Moltrecht","doi":"10.1016/bs.irn.2026.01.014","DOIUrl":"https://doi.org/10.1016/bs.irn.2026.01.014","url":null,"abstract":"<p><p>Biophotons represent ultra-weak light emission (200-800 nm) spontaneously generated by living cells through oxidative metabolic processes, particularly within mitochondria. In 1923, Alexander Gurwitsch demonstrated non-chemical cellular communication in pioneering experiments on what he called 'mitogenetic radiation', which transmitted through quartz but not through glass: it was later confirmed to involve light and especially UV. Since then, this field has evolved to encompass sophisticated detection technologies and theoretical frameworks. Evidence suggests that biophotons, produced mainly by reactive oxygen species (ROS) and excited molecular intermediates during cellular respiration, may serve functional roles in intercellular signalling beyond being mere metabolic byproducts. In neural systems, biophotonic emissions correlate with brain activity, metabolic states, and oxidative stress levels, with emerging applications in neurodegenerative disease monitoring and cognitive assessment. Advanced detection methodologies using photomultiplier tubes (PMT) and electron-multiplying charge-coupled device (CCD) cameras have revealed species-specific spectral signatures and stress-responsive emission patterns. While quantum mechanical explanations remain debated, accumulating evidence supports biophotons as potential biomarkers for cellular health and novel communication pathways. Future therapeutic applications may integrate biophotonic monitoring with photobiomodulation (PBM) interventions for personalized medical treatments.</p>","PeriodicalId":94058,"journal":{"name":"International review of neurobiology","volume":"189 ","pages":"71-104"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148803543","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":"Roadmap update: Sensory neurodegeneration in diabetes.","authors":"Douglas W Zochodne, Maskaki Kobayashi, Prashanth Komirishetty, Aparna Areti","doi":"10.1016/bs.irn.2026.08.018","DOIUrl":"https://doi.org/10.1016/bs.irn.2026.08.018","url":null,"abstract":"<p><p>Human diabetic polyneuropathy (DPN) is a pervasive disabling complication of both types 1 and 2 diabetes mellitus (DM). Here we build on our previous report in this journal, addressing the direct targeting of sensory neurons and the subsequent withdrawal of their distal axon terminals. Specific, albeit largely untested, translational therapeutic approaches are available to 'shore up' the sensory neuron and enable it to regrow its branches. This review provides updated information over several selected pathways our research team has been focused on. We review the evidence for sensory neuron targeting in DM including new human work, specific molecules within neuron perikarya (cell bodies) that foster sensory regeneration and newer ideas on how local nonsystemic targeting of growth cones might also promote regrowth. Our update presupposes important connections between the molecular machinery that supports intact neurons and the capacity of neurons to regrow, reversing DPN deficits. This review is limited in scope but may be a template to investigate the wide repertoire of proteins and noncoding RNAs that might be employed to eventually treat and reverse DPN.</p>","PeriodicalId":94058,"journal":{"name":"International review of neurobiology","volume":"190 ","pages":"55-73"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149019127","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":"Brain energy metabolism changes and neuropsychological impairment in Parkinson disease vs Alzheimer disease.","authors":"Sanaz Khodadadi, Nasim Rezaeimanesh, Ali Ariyae Motahar, Fateme Yousefi, Masoume Avateffazeli, Reyhaneh Montazeri-Shatouri, Elham Hosseini, Sajad Sahab Negah, Abdorreza Naser Moghadasi","doi":"10.1016/bs.irn.2026.06.001","DOIUrl":"https://doi.org/10.1016/bs.irn.2026.06.001","url":null,"abstract":"<p><p>Alzheimer's disease (AD) and Parkinson's disease (PD) are the most common neurodegenerative disorders, posing a significant public health risk. Although they are separate diseases, they have similar neuropsychological characteristics. Despite making up only a small portion of total body mass, the brain requires a disproportionately large amount of energy to maintain neuronal activity, synapse function, and cellular homeostasis. Disruption of energy metabolism is thus a major contributor to neurodegeneration. Energy metabolism has a wide-ranging impact on brain function, including cognitive and psychological processes, and gets increasingly compromised in neurodegenerative disorders. This chapter aims to offer a thorough overview of the link between altered brain energy metabolism and neuropsychological impairment in AD and PD.</p>","PeriodicalId":94058,"journal":{"name":"International review of neurobiology","volume":"188 ","pages":"33-66"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148703020","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":"Brain energy crisis in Alzheimer's and Parkinson's disease: Nanotechnology as a therapeutic strategy.","authors":"Mohini Milmile, Shweta Singh, Ajay Pandey, Gajanan Pawar, Pradnya Petkar, Yogesh Chander, Ranjan Mishra, Ruchi Chawla","doi":"10.1016/bs.irn.2026.05.016","DOIUrl":"https://doi.org/10.1016/bs.irn.2026.05.016","url":null,"abstract":"<p><p>Alzheimer's disease and Parkinson's disease are increasingly recognized as disorders marked not only by protein aggregation but by a sustained failure of brain energy metabolism. Years before overt cognitive or motor symptoms emerge, neurons begin to experience impaired glucose utilization, mitochondrial dysfunction, and declining ATP production. Because the brain is highly energy-dependent, even subtle metabolic disturbances can disrupt synaptic function, impair neuronal signaling, and trigger oxidative stress. As mitochondrial efficiency declines, reactive oxygen species accumulate, inflammatory pathways become chronically activated, and damaged cellular components are insufficiently cleared, creating a vicious cycle that accelerates neurodegeneration. Conventional metabolic therapies, including antioxidants and mitochondrial cofactors, have produced limited clinical success, largely due to poor penetration across the blood-brain barrier and lack of specificity for vulnerable neuronal populations and intracellular targets such as mitochondria. Nanotechnology introduces a more precise therapeutic strategy by enabling targeted delivery of metabolic modulators directly to the brain. Engineered nanocarriers can be designed to cross biological barriers, enhance drug stability, and release therapeutic agents in a controlled or stimuli-responsive manner within diseased regions. Advanced systems including polymeric nanoparticles, lipid-based carriers, intranasal nano formulations, biomimetic vesicles, and catalytic nanozymes offer the ability to simultaneously modulate oxidative stress, restore mitochondrial function, and regulate neuroinflammation. By integrating delivery precision with metabolic intervention, neuro-nanomedicine shifts the therapeutic focus from symptomatic management toward addressing the underlying bioenergetic crisis. Although challenges remain in safety validation, scalability, and clinical translation, targeted nanotherapeutic strategies hold significant promise for transforming the treatment landscape of these debilitating neurodegenerative disorders.</p>","PeriodicalId":94058,"journal":{"name":"International review of neurobiology","volume":"188 ","pages":"231-271"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148703061","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":"Molecular insights of peroxisome proliferator-activated receptor-γ signalling in amyotrophic lateral sclerosis and Huntington's disease.","authors":"Gopika Venu, Vignesh Pandi A, Antony Justin","doi":"10.1016/bs.irn.2026.05.014","DOIUrl":"https://doi.org/10.1016/bs.irn.2026.05.014","url":null,"abstract":"<p><p>Progressive neuronal loss is a hallmark of neurodegenerative diseases like Huntingtons disease (HD) and Amyotrophic lateral sclerosis (ALS) which are caused by convergent mechanisms such as oxidative stress, mitochondrial dysfunction, neuroinflammation, impaired autophagy and dysregulated cell death pathways. Both conditions share significant disruptions in metabolic and inflammatory signalling despite having different genetic origins and clinical manifestations; underscoring the necessity of pathway-oriented treatment approaches. In the central nervous system, peroxisome proliferator-activated receptor-γ (PPAR-γ), a ligand-activated nuclear receptor has become an important regulator of inflammation, redox homeostasis, mitochondrial biogenesis and cellular stress responses. After giving a thorough overview of PPAR-γ structure activation and transcriptional regulation and the PGC-1α-mediated mitochondrial biogenesis axis, this chapter delves deeply into its interactions with major signalling pathways such as NF-κB, Wnt/β-catenin Nrf2/ARE and the autophagy-apoptosis networks. With a focus on experimental data showing PPAR-γ signaling's neuroprotective, anti-inflammatory, antioxidant and metabolic regulatory roles the pathophysiology of ALS and HD is critically investigated. Lastly the need for improved biomarkers, tailored multi-target strategies and selective modulators is highlighted in the discussion of current therapeutic limitations and translational difficulties.</p>","PeriodicalId":94058,"journal":{"name":"International review of neurobiology","volume":"188 ","pages":"113-143"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148703074","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":"Comprehensive insights into Alzheimer's disease: Amyloid-β pathology, tau dysfunction, and neurodegenerative mechanisms.","authors":"Subashchandrabose Chinnathambi, Gomethaga Vairamani Murugan","doi":"10.1016/bs.irn.2026.07.002","DOIUrl":"https://doi.org/10.1016/bs.irn.2026.07.002","url":null,"abstract":"<p><p>Alzheimer's Disease is a terminal, progressive neurodegenerative illness that destroys memory and thought process. The histological hallmark of AD are plaques, found outside of neurons, comprised of amyloid- (A) peptides, and neurofibrillary tangles (NFTs) found within neurons and composed of hyperphosphorylated tau protein. These pathologies of AD cause loss of synaptic function leading to neuronal cell damage and death predominantly in the hippocampus and cerebral cortex. A40 and A42 peptides are generated from the cleavage of amyloid precursor protein (APP) by both-and -secretases although A42 has been reported as more toxic. These oligomers and aggregates of A can reduce synaptic function and also stimulate glial cells, causing oxidative stress and neuroinflammation. Tau is a microtubule-associated protein that keeps the cytoskeleton stable and the cell transportation functioning; during the hyperphosphorylation of tau protein it is released from the microtubules where it aggregates forming NFTs. Once formed the pathological tau can propagate from cell to cell, driving further disease processes. Both A and tau protein have shown synergy to each other; with Amyloid-beta being able to increase tau toxicity to a much greater degree than Amyloid-beta alone. Neuroinflammation continually occurring over many years elevates neurodegeneration by inducing a toxic environment and preventing the removal of damaged proteins from the brain. Some risks associated with the development of Alzheimer's disease (AD) are modifiable (obesity, diabetes, cigarette smoking) while other risks are non-modifiable (age, genetics).</p>","PeriodicalId":94058,"journal":{"name":"International review of neurobiology","volume":"191 ","pages":"1-26"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149042887","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 and glutamine metabolism in neurodegenerative diseases.","authors":"Kesharthini Karthikeyan, Gowshika Velmurugan, Riddhi Upadhyay, Murugan Sevanan, Subashchandrabose Chinnathambi","doi":"10.1016/bs.irn.2026.01.008","DOIUrl":"10.1016/bs.irn.2026.01.008","url":null,"abstract":"<p><p>Glutamate is known as the most important excitatory neurotransmitter in brain. Glutamate and glutamine recycling is very essential to maintain the nitrogen metabolism. Despite of its major functions, its dysregulation is a basic pathology which is common to neurodegenerative diseases such as Parkinson's disease (PD), Alzheimer's disease (AD), and Amyotrophic lateral sclerosis (ALS). Amyloid-β and Tau in AD disrupt glutamate uptake and the glutamate-glutamine cycle, accelerating synaptic failure, whereas loss of astrocytic EAAT2 in ALS generates unrelenting excitotoxicity and motor neuron demise. Toxic α-synuclein aggregation in PD exacerbates dopamine-glutamate imbalance through destabilizing corticostriatal transmission. This review explores on the key mechanisms by which glutamate impairment leads to the pathogenies of neurogenerative disorders and also about current medications like amantadine, memantine, and riluzole which are glutamate antagonists, are shown to partially alleviative but cannot halt the advancement of the disease. One of the potential targets for disease-modifying treatments could be the receptor modulation, astrocytic function, and elimination of excess glutamate.</p>","PeriodicalId":94058,"journal":{"name":"International review of neurobiology","volume":"186 ","pages":"1-24"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148229783","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":"Therapeutic targeting of brain bioenergetics in Alzheimer's disease addressing insulin resistance, glucose hypometabolism, and mitochondrial dysfunction.","authors":"Jatin Jangra, Isha Mahindru, Rajnish Kumar","doi":"10.1016/bs.irn.2026.05.005","DOIUrl":"https://doi.org/10.1016/bs.irn.2026.05.005","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a progressive, age-associated multifactorial neurodegenerative disorder characterised by cognitive decline, synaptic dysfunction, and neuronal loss. Despite over a century of research, effective disease-modifying therapies remain elusive owing to its conundrum pathophysiology. In recent years, AD is increasingly recognised as a complex metabolic disorder characterised by impaired cerebral glucose metabolism, insulin resistance, and mitochondrial dysfunction. These interconnected metabolic disturbances emerge early in the disease state and collectively potentiate other pathologies such as accumulation of amyloid-β (Aβ) plaques, tau hyperphosphorylation, oxidative stress, neuroinflammation, and synaptic dysfunction, thereby establishing bioenergetic failure as a primary factor governing AD progression rather than a downstream phenomenon. While traditional drug development strategies targeting Aβ have failed in clinical trials (limited to monoclonal antibodies), emerging therapeutic models integrating energy failure, thiamine signalling, and insulin-like growth factor (IGF) signalling as upstream events show significant promise in countering downstream neurodegeneration. This chapter summarises the mechanistic framework linking bioenergetic breakdown to AD pathology, with potential therapeutic opportunities aimed at restoring mitochondrial function, enhancing glucose utilisation, and correcting insulin signalling, further opening new avenues for multimodal interventions and identification of progressive metabolic dysfunction biomarkers to aid diagnostic processes.</p>","PeriodicalId":94058,"journal":{"name":"International review of neurobiology","volume":"187 ","pages":"91-132"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148440432","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}