ABSTRACT:Transcription factors have been employed to reprogram one type of cells into a different type of cells, an approach commonly called cell transdifferentiation. Astrocyte-to-neuron conversion is one type of cell transdifferentiation, where neural transcription factors are overexpressed in astrocytes to convert them into neurons. Many neural transcription factors, such as NeuroD1, Ascl1, Ngn2 and various combinations, have been demonstrated to successfully convert astrocytes into neurons both in vitro and in vivo, opening a new avenue for neural regeneration using internal glial cells. While significant progress has been made using in vivo astrocyte-to-neuron conversion approach to regenerate functional new neurons and repair damaged neural circuits, challenges also arise regarding how to identify genuine cell conversion. Here, I review critical steps during astrocyte-to-neuron conversion process, from initial expression of neural transcription factors in astrocytic nuclei to transitional stage in-between astrocytes and neurons, and eventual acquisition of mature neuronal properties. This review provides a general guideline on how to identify genuine astrocyte-to-neuron conversion with comprehensive approaches.
ABSTRACT:Axonal dysfunction is a critical event in neurodegenerative diseases, which can precede neuronal loss. For instance, in multiple sclerosis, chronic demyelination leads to axonal transection and downstream neurological deficits, yet in other neurodegenerative conditions, the causal relationship between axonal pathology and disease progression remains elusive. While defects in axonal transport, cytoskeletal integrity, and organelle trafficking are observed in Alzheimer's disease and the frontotemporal dementia-amyotrophic lateral sclerosis spectrum, a question remains: Are axonal defects merely downstream consequences of somatic neurodegeneration, or do they actively drive pathogenesis? Emerging evidence suggests that early axonal dysfunction may accelerate disease progression through disrupted connectivity, retrograde degeneration, and neuroinflammation. Here, we highlight current evidence on axonal pathophysiology across Alzheimer's disease and frontotemporal dementia-amyotrophic lateral sclerosis. We first outline the makeup of the mature axonal compartment, as well as the processes related to axonal maintenance, which include myelination, glial support, and microtubule-dependent transport mechanisms. We further compare axonal perturbations in Alzheimer's disease and frontotemporal dementia-amyotrophic lateral sclerosis, exploring commonalities as potential convergent mechanisms. Therapeutic strategies to stabilize axons by maintaining microtubule dynamics, restoring energetics, or modulating glial support could therefore theoretically offer neuroprotection if performed selectively on vulnerable neuronal subsets and early in the disease course. Ultimately, by reframing axonal pathology as a primary driver rather than an epiphenomenon, this review underscores the importance of targeting axonal health in neurodegenerative diseases.
ABSTRACT:Inherited retinal degenerative diseases, such as retinitis pigmentosa, cause progressive photoreceptor loss and irreversible vision decline, yet effective treatments remain unavailable. Our previous studies demonstrated that Lycium barbarum glycopeptide delays photoreceptor degeneration in a chemically induced retinitis pigmentosa model, primarily through antiinflammatory mechanisms. In this study, we extended these findings to an inherited retinitis pigmentosa model to further elucidate the neuroprotective actions of Lycium barbarum glycopeptide. Lycium barbarum glycopeptide was orally administered daily to rd10 mice beginning at postnatal day 8, prior to photoreceptor degeneration, and retinal function and morphology were evaluated at postnatal day 25, the peak of rod apoptosis. Behavioral assays, electroretinography, immunofluorescence staining, proteomic profiling, and western blotting were performed to assess the therapeutic effects and molecular mechanisms of Lycium barbarum glycopeptide. Lycium barbarum glycopeptide treatment significantly improved visual performance in rd10 mice, as shown by enhanced optomotor responses and black.white transition behavior. Electroretinography analysis revealed increased scotopic a-wave amplitudes, indicating improved photoreceptor function. Histological evaluation showed preservation of outer nuclear layer thickness and maintenance of rod and cone opsin expression. Lycium barbarum glycopeptide also reduced microglial and Muller glial activation in a region-dependent manner. Proteomic and biochemical analyses revealed that Lycium barbarum glycopeptide upregulated key phototransduction proteins while concurrently downregulating pro-inflammatory mediators such as interleukin-6, nuclear factor kappa B, cyclooxygenase-2, and tumor necrosis factor-α. Collectively, these results demonstrate that Lycium barbarum glycopeptide protects against inherited photoreceptor degeneration by improving retinal function and structure, alleviating neuroinflammation, and supporting phototransduction recovery. This work extends our previous findings and highlights Lycium barbarum glycopeptide as a promising therapeutic candidate for inherited retinal degenerative diseases.
Long-term regular exercise is effective against age-related cognitive decline. However, the mechanisms through which mind-body exercises such as Tai Chi produce these effects, and the involvement of exosome-mediated signaling between the periphery and the brain, are unknown. For this 1:1 matched observational study, cognitively normal participants aged 60 to 75 years, with a male-to-female ratio of 2:3, were recruited into the long-term regular Tai Chi group (n = 50) and long-term irregular exercise group (n = 50). N-back task functional magnetic resonance imaging revealed that the long-term regular Tai Chi group showed a better working memory performance than the long-term irregular exercise group. Moreover, the long-term regular Tai Chi group showed altered activation in the superior frontal gyrus and pre/postcentral gyri. By integrating microRNA sequencing and proteomic profiling of serum exosomes, we identified miR-625-5p as a significant differential factor targeting CALM1 and VDAC2, whose expression levels negatively correlated with 1-back task accuracy. To investigate causality, serum-derived exosomes from both groups were delivered intravenously to SAMP8 mice. Exosomes from the Tai Chi group improved working memory deficits and resulted in an increase in prefrontal dendritic spine density, while down-regulating miR-625-5p and up-regulating the synaptic plasticity-related proteins calmodulin 1 and voltage-dependent anion channel 2 in the prefrontal cortex. Collectively, our findings suggest that long-term Tai Chi exercise may improve cognitive function by remodeling circulating exosome cargo. The key mediator, miR-625-5p, may act via the calmodulin 1/voltage-dependent anion channel 2 pathway to orchestrate prefrontal synaptic remodeling. Exosomes derived from Tai Chi practitioners may be a potential therapy for age-related cognitive decline.
Limb deformities have a close pathological link with peripheral nerve injuries; however, there is currently a lack of analysis and summary of research trends in this field aimed at elucidating the close relationship between limb deformities and peripheral nerve repair. Based on the Web of Science Core Collection database, this study retrieved 897 articles published between 2001 and 2025. A bibliometric analysis using CiteSpace and VOSviewer was therefore conducted to comprehensively map the research landscape, hotspots, and evolving trends in this field, revealing a sustained annual upward trend in research output. The University of Washington (UW, Seattle) was the institution with the most publications and the greatest impact. The Journal of Pediatric Orthopaedics was the journal with the most publications, while the Journal of Bone and Joint Surgery-American Volume was the journal with the greatest academic impact. Keyword analysis identified two major clusters of interest: diabetic peripheral neuropathy and foot deformities, involving studies on Charcot neuroarthropathy, diabetic foot ulcers, and amputation prevention; and birth-related brachial plexus palsy and its secondary shoulder and elbow deformities, focusing on functional reconstruction strategies such as tendon transfer and osteotomy. Burst keyword analysis revealed a clear shift in the research focus. From 2003 to 2013 (the early period), studies primarily focused on single-site functional impairments and conservative treatments (such as botulinum toxin). From 2014 to 2025 (the recent period), the focus shifted toward investigating "prevalence" and "risk factors," as well as conducting in-depth studies on "reconstructive" surgery, diabetic foot ulcers, and molecular mutation mechanisms. Current research in this field focuses on the bidirectional relationship between "malformations" and "nerves," exploring how nerve injuries cause malformations and investigating secondary nerve compression and damage following malformations. Peripheral neuropathies, such as diabetic peripheral neuropathy, Charcot-Marie-Tooth disease, and obstetric brachial plexus palsy, are the key direct or indirect causes of specific limb deformities (such as foot deformities, talipes, and forearm supination deformities). Research on the mechanical effects of deformities on nerves focuses on how skeletal deformities (such as elbow valgus/varus or knee valgus) result in or exacerbate nerve entrapment syndromes (such as ulnar nerve or common peroneal nerve injuries) through abnormal biomechanical mechanisms (such as excessive traction or dynamic compression). During surgeries for correcting complex deformities, the use of intraoperative nerve monitoring provides real-time early warning to avoid iatrogenic brachial plexus injuries and ensure patient safety, which has become a prominent technical focus. Previous studies have established the criteria for early monitoring of shoulder deformities and Mallet functional assessment following obstetric paralysis. Research over the past 5 years has focused on the mechanisms by which deformities exert mechanical effects on nerves, as well as the application of precision surgical techniques and intraoperative nerve monitoring. Surgical repair strategies for cubital tunnel syndrome and ulnar nerve palsy-induced claw hand are also among the key clinical areas of interest. Overall, these findings indicate that research on limb deformities associated with peripheral neuropathy and injury repair has evolved into two major research domains, focusing on nerve repair for deformities caused by diabetic peripheral neuropathy and limb deformities resulting from obstetric paralysis. Current research trends are moving toward precision, minimally invasive approaches, and multidimensional efficacy assessments. Future research should deepen the understanding of the "deformity-nerve" interaction mechanisms, focus on early warning systems, intraoperative nerve monitoring, and individualized functional reconstruction, and thereby improve patient outcomes and surgical safety.
The regulatory network of the spleen, a densely innervated immune hub, undergoes pathological remodeling following spinal cord injury. Whether targeted electrical stimulation of the spleen at specific frequencies can reverse peripheral immune suppression or improve the central immune system remains unclear. The aim of this study was to elucidate the previously unexamined effects and differential regulatory mechanisms of transsplenic apex electrical stimulation (10, 50, and 100 Hz) on peripheral immune suppression and spinal cord homeostasis after spinal cord injury. A mouse model of T3 spinal cord injury was established and systematically evaluated through functional assessments, splenic/spinal cord transcriptome sequencing, weighted gene co-expression network analysis, Short Time-series Expression Miner analysis, and multiomics validation to investigate the frequency-dependent effects of stimulation. The effects of the electrical stimulation exhibited significant frequency dependence. Specifically, 100 Hz electrical stimulation effectively restored the impaired bacterial clearance capacity in the host (P < 0.001), reversed the suppression of adaptive immune-related gene modules in the spleen, and shifted immune responses toward T helper 17 (Th17) cell-axis remodeling. This was accompanied by upregulation of the expression of key hub genes such as those encoding integrin alpha x, CC chemokine receptor 6, Fc receptor-like 5, leukocyte immunoglobulin-like receptor subfamily A member 5, and Th17 signature cytokines such as interleukin-17, interleukin-23, and transforming growth factor-beta. In the spinal cord, 100 Hz electrical stimulation suppressed pro-inflammatory pathways such as nuclear factor-kappa B and tumor necrosis factor-alpha while activating neurorepair pathways, such as glutamatergic synapses. In contrast, 10 Hz electrical stimulation failed to alleviate peripheral immune suppression and exacerbated splenic immunosuppression and central neuroinflammation. These findings demonstrate that electrical stimulation of the splenic apex exerts frequency-dependent, bidirectional modulatory effects, with 10 and 100 Hz eliciting contrasting neuroimmune responses. Specifically, 100 Hz electrical stimulation activates the splenic Th17 immune axis, offering a potential mechanism to reverse spinal cord injury-induced immunodeficiency and neurological damage. Identifying the stimulation frequency as a critical therapeutic variable provides a foundation for developing frequency-optimized integrated neuroimmunomodulatory strategies for the treatment of spinal cord injury.
Communication between astrocytes and microglia establishes a basis for maintaining cellular homeostasis, metabolic processes, and injury response in the central nervous system. Activation of astrocytes and microglia is a major initial phase of the response of the organism to pathogenic conditions that facilitate immune response causing neuroinflammation. The neuroprotective effects of neuroinflammation manifest in various contexts, including trauma, aging, and neurodegeneration. However, chronic glial reactivity can become a source of progressive central nervous system damage and suppress neuroprotective functions, ultimately exacerbating neurodegenerative diseases. In this scenario, signal transduction by glial cells, combined with mitochondrial dysfunction, leads to the establishment of a self-sustaining cycle of inflammation and metabolic stress. Modulating glial reactivity, correcting mitochondrial impairments, and targeting immune signaling pathways may offer a potential therapeutic strategy. Such interventions could involve suppressing excessive mitochondrial fission and targeting key molecular pathways, including nuclear factor kappa-light-chain-enhancer of activated B cells, mammalian target of rapamycin, and immune receptors such as triggering receptor expressed on myeloid cells 2. The primary goal of such approach would not be complete suppression of neuroinflammation but rather the restoration of balance between pro-and anti-inflammatory programs, promoting the transition of glial cells toward neuroprotective phenotypes that slow neurodegenerative progression.
The role of the locus coeruleus in aging and neurodegenerative diseases has recently attracted attention. There is growing evidence of changes in the locus coeruleus-norepinephrine system in aging and neurodegenerative diseases, including increased tau accumulation, an inverted U-shaped pattern in the neuromelanin signal, and altered functional connectivity. This review summarizes the research applications and advancements in the study of cognitive aging and dysfunction of the locus coeruleus-norepinephrine system in neurodegenerative diseases. Recent evidence has suggested pathologic protein accumulation, locus coeruleus degeneration, reduced neuromelanin signal, and altered functional connectivity in neurodegenerative diseases in both human and animal models. Notably, the specific regions affected and the severity of these changes can vary subtly among different neurodegenerative disorders. Additionally, recent studies have shown a link between alterations in the locus coeruleus-norepinephrine system and both Alzheimer's and Parkinson's diseases. The possible mechanisms include promoting pathological protein accumulation, pro-inflammatory responses, synaptic plasticity dysfunction, oxidative stress, and blood- brain barrier dysfunction. Advanced experimental technologies have recently been applied to investigate the role of the locus coeruleus-norepinephrine system in aging, Alzheimer's disease, and Parkinson's disease. These advanced technologies, including optogenetic or chemogenetic methods and omics analysis help uncover the effects of specific locus coeruleus activation patterns and the locus coeruleus-related circuit mechanisms underlying its vulnerability during aging and neurodegenerative diseases. Thus, therapies targeting the locus coeruleus-norepinephrine system, including drugs and vagus nerve stimulation, have the potential for clinical application. Many studies have demonstrated the effects of adrenoreceptor-targeted drugs on cognitive function and Parkinson's disease, although some showed no effects. Limited data are available for norepinephrine-targeted drugs, which have demonstrated less-than-ideal results. Recent studies have demonstrated that vagus nerve stimulation can improve cognitive function in Alzheimer's disease and reduce the symptoms of Parkinson's disease, including gait function, suggesting that vagus nerve stimulation could be a new supplementary treatment for neurodegenerative diseases. Overall, the evidence reviewed suggests that the locus coeruleus-norepinephrine system is disrupted during aging and neurodegenerative diseases, and that this disruption can aggravate disease progression. Thus, the locus coeruleus-norepinephrine system is a potential therapeutic target in slowing disease progression. Future studies should focus on the locus coeruleus-norepinephrine system and use advanced experimental and neuroimaging technologies to reveal early pathological alterations and the underlying mechanisms of its vulnerability during aging and neurodegenerative diseases, along with exploring potential therapeutic approaches.
Parkinson's disease is a major neurodegenerative disorder, and mitochondrial dysfunction has been increasingly recognized as a key contributor to its pathogenesis. Recent studies suggest that treatment with mesenchymal stem cell-derived small extracellular vesicles offers a promising cell-free strategy for mitigating neurodegeneration. In the present study, we investigated the effects of induced pluripotent stem cell-derived mesenchymal stem cell-derived small extracellular vesicles on dopaminergic neurons in a murine Parkinson's disease model and explored the underlying mechanisms related to mitochondrial impairment. A Parkinson's disease mouse model was established using 1-methyl-4-phenyl-1,2,4,5- tetrahydropyridine-induced neurotoxicity, followed by the intranasal administration of mesenchymal stem cell-derived small extracellular vesicles and comprehensive behavioral and pathological assessments. To elucidate the mechanistic basis of any effects, we examined mitochondrial function and Homer protein homolog 3 (Homer3) expression in brain tissue. Mice with Homer3 knockdown were used to validate the role of Homer3 in the therapeutic effects of mesenchymal stem cell-derived small extracellular vesicles. Mesenchymal stem cell-derived small extracellular vesicle administration significantly reduced motor dysfunction in 1-methyl-4-phenyl-1,2,4,5-tetrahydropyridine-induced Parkinson's disease mice by protecting dopaminergic neurons. Furthermore, mesenchymal stem cell-derived small extracellular vesicles increased both mitochondrial number and function through Homer3 upregulation in Parkinson's disease mice. The therapeutic benefits of mesenchymal stem cell-derived small extracellular vesicles in rescuing dopaminergic neurons were impaired by Homer3 knockdown. Collectively, these findings suggest that, at least in part, mesenchymal stem cell-derived small extracellular vesicles ameliorate dopaminergic neuron damage via the Homer3-mediated restoration of mitochondrial function in a mouse model of Parkinson's disease. Our results highlight the neuroprotective role of mesenchymal stem cell- derived small extracellular vesicles in Parkinson's disease and provide new perspectives on their therapeutic potential.
Optic nerve injury induces rapid retinal neurodegeneration; however, how distinct retinal cell type responses are coordinated from the hyperacute injury phase to the early repair phase remains incompletely understood. In this study, to explore the dynamic changes in intercellular and intracellular signaling events between different cell types and elucidate their potential roles in retinal ganglion cell survival and early repair, we generated a time-resolved single-nucleus RNA sequencing atlas of adult male mouse retinas across five hyperacute-to-acute timepoints (2 hours, 8 hours, 1 day, 3 days, and 7 days) following optic nerve injury. Using computational network analysis, we reconstructed dynamic cell-to-cell communication and subsequent internal genetic responses among retinal ganglion cells, Müller glia, microglia, and endothelial cells. Distinct stage-specific intercellular communication networks were identified, including transient Itgb1-associated signaling between Müller glia and retinal ganglion cells that peaked at early timepoints, enhanced Nrxn1-Nlgn1-mediated signaling in endothelial cells during the acute phase, and sustained Sema6a-Plxna4 interactions in microglia through day 7. Functional pathway analysis linked these signaling events to focal adhesion, energy metabolism, immune regulation, and cell adhesion pathways. Multiplex immunofluorescence further validated the temporal dynamics and spatial localization of key signaling molecules, including Itgb1, Nlgn1, and Plxna4, consistent with the transcriptomic findings. Collectively, these results delineate a coordinated hyperacute-to-acute neuro-glial-vascular signaling network that supports retinal ganglion cell survival and identify potential molecular targets for therapeutic intervention following optic nerve injury.
Chimeric antigen receptor-engineered cell therapies provide a novel therapeutic approach for refractory neuroimmune disorders. These cell products penetrate deep into tissue and achieve long-term depletion of pathogenic B cells and plasma cells, supporting sustained immune tolerance and durable clinical remission. Chimeric antigen receptor-T cells, chimeric antigen receptor-natural killer cells, chimeric autoantigen receptor T cells, and chimeric antigen receptor-regulatory T cells selectively target and eliminate pathological immune effectors, reduce autoantibody levels, and help maintain long-term remission in multiple sclerosis, myasthenia gravis, neuromyelitis optica spectrum disorder, chronic inflammatory demyelinating polyneuropathy, and autoimmune encephalitis. This review summarizes the therapeutic advance of chimeric antigen receptor-based cell therapies for neuroimmune disorders. Growing clinical evidence indicates that CD19-directed and B-cell maturation antigen-directed chimeric antigen receptor-T cells provide rapid and persistent clinical improvement even in patients with multiple prior treatment failures, accompanied by depletion of the B-cell lineage and sustained reduction in autoantibody titers. Key mechanisms include enhanced access across the blood-brain barrier, targeted lysis of tissue-resident memory B cells and long-lived plasma cells, and subsequent immune repertoire reconstitution. Important challenges remain incompletely defined, including long-term safety, late relapse, high manufacturing expenses, and restricted availability of autologous cell products. Further advances will require optimized chimeric antigen receptor architectures, off-the-shelf allogeneic platforms, and validation in large controlled clinical trials. This review presents a structured framework for future progress and highlights chimeric antigen receptor based immunotherapy as a pivotal strategy that replaces long term immunosuppression with durable drug free remission, thus reshaping the standard treatment model and redefining therapeutic goals for patients with neuroimmune disorders.
The heterogeneous nuclear ribonucleoprotein-associated protein Raly plays a role in regulating cell proliferation and metabolism in eukaryotic nerve cells. However, the biological significance of Raly in oligodendrocyte lineage progression has not been previously explored. In this study, we found that Raly expression decreased during maturation of oligodendrocyte lineage cells. Knockdown of Raly in primary oligodendrocyte progenitor cells cultured in differentiation medium resulted in a significant increase in myelin-related proteins myelin basic protein and MAG. Furthermore, injection of an adenovirus expressing Raly shRNA into the subventricular zone of mice promoted oligodendrocyte progenitor cell differentiation, restored white matter integrity, and ameliorated cognitive deficits in the bilateral common carotid artery stenosis and senescence model. We further investigated the mechanism by which Raly regulates oligodendrocyte progenitor cell differentiation. Downregulation of Raly in primary oligodendrocyte progenitor cells led to increased mRNA and protein levels of Sox10, a pivotal player in oligodendrocyte development. The stability of Sox10 mRNA was unaffected by Raly downregulation, and RNA immunoprecipitation assays showed no binding between Raly and Sox10 mRNA. Dual luciferase and chromatin immunoprecipitation assays revealed that Raly downregulated the transcription of Sox10 by binding to a site located 1200 bp upstream of the Sox10 start codon. Collectively, our findings suggest that Raly plays a crucial role in oligodendrocyte progenitor cell differentiation and negatively regulates Sox10. These results may provide new insights into therapeutic strategies for neurological disorders associated with hypomyelination.
The pro-inflammatory aldehyde acrolein has long been implicated as a critical factor in the pathology of multiple sclerosis. Given that acrolein can be scavenged via the endogenous enzyme aldehyde dehydrogenase 2 (ALDH2), we sought to investigate whether individuals with an ALDH2 deficiency, ALDH2*2, may be more susceptible to worsened symptoms of multiple sclerosis. In this study, we model this clinically relevant genotype in mice with an animal model of multiple sclerosis, experimental autoimmune encephalomyelitis. Our results indicate that ALDH2*2 mice induced with experimental autoimmune encephalomyelitis not only display heightened behavioral deficits and neuropathic pain, but also enhanced expression of acrolein, various inflammatory markers, glutamate transporter dysfunction, demyelination, and a trend of neuronal loss, demonstrating a neuroprotective role of ALDH2 on various key aspects of multiple sclerosis pathology. Notably, these differences were absent between control ALDH2*2 and wild-type mice, indicating that the ALDH2*2 genotype alone does not appear to produce behavioral or physiological deficits. However, our results support emerging studies suggesting that individuals with ALDH2*2 may suffer from worsened symptoms in an acrolein-mediated disease such as multiple sclerosis compared with individuals with functioning ALDH2. This study additionally serves to reinforce the pivotal role of acrolein and ALDH2 in experimental autoimmune encephalomyelitis pathogenesis, expanding the possible therapeutic targets to achieve neuroprotection in multiple sclerosis.
Alzheimer's disease is a formidable health challenge due to lack of effective therapeutic modalities. The excitation/inhibition imbalance in the early stage of Alzheimer's disease can be potentially considered as a central link between structural brain pathology and cognitive dysfunction. However, the role and effects of reactive astrocytes in the neuronal excitability in early Alzheimer's disease remain unclear. Here, we present a tripartite synaptic model integrating the interactions between neurons and astrocytes than can clarify the role of astrocytes in the regulation of excitation/inhibition. Our model integrates the cation channel transient receptor potential ankyrin 1, whose activation triggers calcium influx, thereby enhancing the fidelity of astrocyte calcium dynamics. Constrained by physiological data, we demonstrate that amyloid-β can activate astrocytes to release glial neurotransmitters, thereby mediating the hyperexcitability of nearby neurons. We also investigate the astrocyte-mediated symbiosis of two neurotransmitters, glutamate and gamma-aminobutyric acid, at the glutamatergic synapse in the context of Alzheimer's disease, to predict the inhibitory compensatory response to excitotoxicity. During excitotoxicity, astrocytes can use the coupling of the excitatory amino acid transporter and gamma-aminobutyric acid transporter to control the concentration ratio of glutamate and gamma-aminobutyric acid in the synaptic cleft, and may convert both through the intracellular gamma-aminobutyric acid synthesis pathway. Our findings reveal that the coding efficiency of neurons diminished as the effects of amyloid-β deepened, establishing a direct link between the pathological features of Alzheimer's disease and cognitive dysfunction. These simulations suggest that astrocytes play a critical role in regulating the neuronal excitation/inhibition balance in the early stage of Alzheimer's disease, thereby influencing the subsequent processes of information transmission, learning, and memory. The pathways characterized by our model present potential therapeutic targets for Alzheimer's disease.
