Mann GS, Gadelmawla AF, Dway A
… +8 more, Fayaz FH, Kebede EA, Varadharaj NK, Akram A, Khan A, Azuwike UB, Sampangi BK, Ogundijo OA
Neuroscience
· 2026 Aug · PMID 42229830
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BACKGROUND: Tourette syndrome (TS) involves motor and vocal tics, often with obsessive-compulsive disorder (OCD) and attention-deficit/hyperactivity disorder (ADHD). Cannabis-based medicines (CBMs) are a potential therap...BACKGROUND: Tourette syndrome (TS) involves motor and vocal tics, often with obsessive-compulsive disorder (OCD) and attention-deficit/hyperactivity disorder (ADHD). Cannabis-based medicines (CBMs) are a potential therapy due to their interaction with the endocannabinoid system, potentially reducing tics and associated symptoms. Compared to antipsychotics, CBMs may offer improved tolerability and fewer side effects. Although evidence is limited, emerging studies suggest their potential to improve quality of life in TS. This review was registered with PROSPERO (CRD420251088633). AIM: To evaluate the effectiveness of CBMs in treating TS. METHODS: We systematically searched PubMed, Google Scholar, ScienceDirect, and the Cochrane Collaboration Database for cohort studies and randomized controlled trials (RCTs) up to July 2, 2025. Data extraction included study characteristics and efficacy outcomes measured by the Yale Global Tic Severity Scale (YGTSS) and Premonitory Urge for Tics Scale (PUTS). Meta-analysis using Review Manager 5.4 compared pre- and post-treatment scores using mean difference (MD) and 95% confidence intervals (CI). RESULTS: From 1,105 screened articles, eight studies met inclusion criteria for the review, and seven were included in the meta-analysis, involving 306 adult TS patients. CBMs significantly reduced YGTSS scores (MD = - 13.29, 95% CI [-21.67 to - 4.91], P = 0.002) and PUTS scores (MD = - 4.09, 95% CI [-7.24 to - 0.93], P = 0.01). CONCLUSION: CBMs show promising potential in reducing tics and premonitory urges in TS. Larger, placebo-controlled trials are needed to confirm efficacy, ensure safety, and optimize dosing.
Neuroscience
· 2026 Aug · PMID 42229829
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Spaced contextual fear conditioning can establish a memory that no longer requires contribution from the hippocampus (HPC). It is unclear, however, whether spaced conditioning episodes alone are sufficient or whether a c...Spaced contextual fear conditioning can establish a memory that no longer requires contribution from the hippocampus (HPC). It is unclear, however, whether spaced conditioning episodes alone are sufficient or whether a combination of spaced episodes and a high saliency unconditioned stimulus are required to make the context fear memory become HPC independent. To address this, rats underwent spaced contextual fear conditioning with shocks of low (0.4 mA), intermediate (0.7 mA), or high (1.0 mA) saliency, followed by sham or neurotoxic HPC lesions. Two weeks later, retention was assessed using freezing as the memory index, and c-Fos expression was quantified to identify supporting brain structures. In the low-saliency condition, control rats exhibited minimal freezing, limiting interpretation of lesion effects. With intermediate saliency, control rats froze robustly, whereas HPC-lesion rats did not, suggesting maintained HPC dependence despite spaced learning. In contrast, high-saliency conditioning produced comparable freezing in both groups, suggesting that combining spaced episodes with a strong stimulus creates an HPC-independent memory. Consistent with behavior, c-Fos analysis revealed increased expression in perirhinal and anterior cingulate cortices across conditions, regardless of saliency or lesion effects, implicating these regions in context representation. Elevated c-Fos was observed in the basolateral amygdala in rats from the spaced condition that retained fear memory, including HPC-lesioned rats, supporting its role in fear representation. Thus, HPC-independent contextual fear memory emerges when spaced conditioning is paired with a highly salient stimulus and is supported by a perirhinal and anterior cingulate cortices context representation and an amygdalar fear representation.
Kuramitsu A, Sugiyama S, Ikegame Y
… +6 more, Yano H, Shinoda J, Ohi K, Shioiri T, Nishihara M, Inui K
Neuroscience
· 2026 Aug · PMID 42229828
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The 40-Hz auditory steady-state response (ASSR) reflects gamma-band oscillations and has been proposed as a candidate biomarker for psychiatric disorders. Previous work has shown that novelty detection related to tempora...The 40-Hz auditory steady-state response (ASSR) reflects gamma-band oscillations and has been proposed as a candidate biomarker for psychiatric disorders. Previous work has shown that novelty detection related to temporal and physical stimulus features can modulate the magnitude of the 40-Hz ASSR. The present study examined whether spatial novelty induced by interaural time differences modulates the 40-Hz ASSR in parallel with transient auditory evoked responses. Magnetoencephalography recordings were obtained from 23 healthy participants while listening to binaural auditory stimuli presented at 40 Hz and lateralized to the left or right by interaural time differences in a pseudo-random sequence. Trials were classified according to whether the preceding stimulus was presented on the same or a different side, and further divided based on the number of preceding stimuli. Spatial novelty modulated the N100m, with larger amplitudes observed following stimuli on a different side and a graded increase with the number of preceding different stimuli. In contrast, neither the power nor phase synchronization of the 40-Hz ASSR was influenced by spatial novelty. These findings suggest that the sensitivity of the 40-Hz ASSR to novelty may depend on the dimension of stimulus change and may not directly mirror novelty-related activity reflected in the N100m.
Wang Z, Zhu J, Zhu S
… +4 more, Dai Z, Wu L, Fu Q, Jiang Y
Neuroscience
· 2026 Jun · PMID 42229827
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BACKGROUND: Ischemic stroke carries a significant risk of recurrence. Identifying individuals at highest risk for multiple recurrences is crucial for optimizing secondary prevention strategies. METHODS: In this prospecti...BACKGROUND: Ischemic stroke carries a significant risk of recurrence. Identifying individuals at highest risk for multiple recurrences is crucial for optimizing secondary prevention strategies. METHODS: In this prospective cohort study, we enrolled 5,415 patients with first-ever ischemic stroke. Subjects (N = 5,040) were followed up quarterly for 2.5 years. We documented the occurrence and timing of any recurrent ischemic stroke events, along with medication adherence. RESULTS: Over the follow-up period, 425 patients (8.43%) experienced at least one recurrence. Among these, 365 had a single recurrence (7.24%) and 60 had multiple recurrences (≥2 events). A significantly shorter mean time to first recurrence was observed in the multiple-recurrence group compared to the single-recurrence group (11.77 ± 9.50 vs. 17.19 ± 12.46 months, P = 0.008). Multivariable logistic regression confirmed time to first recurrence as an independent predictor of multiple recurrences (adjusted OR 0.965 per month increase, 95% CI: 0.933-0.998, P = 0.036). Using receiver operating characteristic analysis, a time-to-first-recurrence threshold of 6.65 months was identified. Using receiver operating characteristic analysis, a time-to-first-recurrence threshold of 6.65 months was identified. Recurrence within this cutoff was significantly associated with an increased risk of subsequent multiple strokes (adjusted OR for longer time to recurrence (OR 0.704, 95% CI: 0.535-0.927, P = 0.012). CONCLUSIONS: In our cohort, one in seven patients with a recurrent stroke went on to experience multiple recurrences. An early first recurrence, particularly within 6.65 months of the index stroke, is a strong predictor of this high-risk pattern. These patients warrant prioritized and intensified secondary prevention management.
Ibitoye RT, Bancroft MJ, Hamilton A
… +3 more, Bronstein AM, Werring DJ, Kaski D
Neuroscience
· 2026 Jun · PMID 42229826
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Cerebral small vessel disease (cSVD) is a common, potentially modifiable cause of poor balance control and falls in older people, but its early effects on balance control are difficult to detect. In this exploratory stud...Cerebral small vessel disease (cSVD) is a common, potentially modifiable cause of poor balance control and falls in older people, but its early effects on balance control are difficult to detect. In this exploratory study, 20 older people with a broad range of cSVD on head MRI scans (median age 74.5 years, interquartile range 68-79 years) had their balance perturbed by motorised pulls at the shoulder. Body movements, ground reaction forces and prefrontal functional near-infrared spectroscopy (fNIRS) haemodynamic responses were recorded. Head MRI scans were reviewed to produce a score of cSVD burden ranging from 0 to 7 points based on lacunes (0-3), white matter hyperintensities (0-3), and cerebral microbleeds (0-1). Participants were divided into "low" (0-2 points) and "moderate" (3-7 points) cSVD burden subgroups, each of 10 participants. Moderate vs. low cSVD burden associated with worse cognitive function. Balance and gait measures (Short Physical Performance Battery test score, tandem walking, stepping responses to manual retropulsion) were similar in the two cSVD burden groups, as were pull-related body sway and resisting ground reaction forces. More cSVD associated with less pull force to induce steps, and with greater balance-related fNIRS prefrontal cortical haemodynamic responses. Prefrontal cortical activation was the most significant measure, explaining 33% of the variation in cSVD burden, while the stepping force threshold explained 17%. Our results suggest that, in addition to cognition, prefrontal cortical responses and stepping force thresholds are likely sensitive to effects of cSVD.
Deep brain stimulation (DBS) is an emerging therapy for treatment-resistant neurological and psychiatric disorders. Despite this, little is known about the anatomical and functional mechanisms that underlie this therapy....Deep brain stimulation (DBS) is an emerging therapy for treatment-resistant neurological and psychiatric disorders. Despite this, little is known about the anatomical and functional mechanisms that underlie this therapy. We targeted DBS to white matter adjacent to the subcallosal anterior cingulate cortex (SCC-DBS) in macaques, modeling the approach proven effective for depression in humans. SCC-DBS caused a selective increase in fractional anisotropy, linked to white matter microstructure, in the cingulum bundle. At the cellular level, this was associated with an increase in both myelinated oligodendrocytes and the degree of myelination in the mid-cingulum bundle. SCC-DBS also altered brain-wide functional connectivity, changing interactions between the SCC and multiple brain networks, most notably the default mode network that has been implicated in depression. Overall, our data indicate that white matter remodeling as well as selective changes in multiple brain networks may contribute to DBS's therapeutic efficacy.
Human immunodeficiency virus 1 (HIV-1) infection often results in sensory neuropathy, with >60% of affected individuals developing chronic pain. Although viral proteins such as glycoprotein 120 (gp120) contribute to neur...Human immunodeficiency virus 1 (HIV-1) infection often results in sensory neuropathy, with >60% of affected individuals developing chronic pain. Although viral proteins such as glycoprotein 120 (gp120) contribute to neuronal injury and pain hypersensitivity, their specific effects on nociceptive signaling remain unclear. Hyperactivity of -methyl-d-aspartate receptor (NMDAR) in the spinal dorsal horn is a hallmark of neuropathic pain. Here, we determined how gp120 affects synaptic NMDAR activity in spinal excitatory and inhibitory neurons in male and female mice. Intrathecal gp120 enhanced expression of α2δ-1 and GluN1 in the dorsal root ganglion (DRG) and spinal cord. Gp120 also increased α2δ-1-GluN1 interaction and their synaptic trafficking in the spinal cord. Functionally, gp120 induced hyperactivity of presynaptic NMDARs on primary afferent terminals and postsynaptic NMDARs in vesicular glutamate transporter 2-expressing excitatory, but not vesicular GABA/glycine transporter-expressing inhibitory, dorsal horn neurons. Importantly, gp120-induced hyperactivity of both presynaptic and postsynaptic NMDARs was eliminated by the α2δ-1 inhibitory ligand gabapentin or by an α2δ-1 C-terminal peptide that disrupts α2δ-1-NMDAR interactions. Correspondingly, treatment with the NMDAR antagonist, gabapentin, or α2δ-1 C-terminal peptide consistently reversed gp120-induced persistent nociceptive hypersensitivity. Furthermore, genetic deletion of or selective ablation of GluN1 in DRG neurons significantly attenuated gp120-induced nociceptive hypersensitivity. Together, these findings indicate that gp120 drives nociceptive hypersensitivity by augmenting presynaptic and postsynaptic activity of α2δ-1-bound NMDARs, thereby amplifying nociceptive transmission from primary afferents to spinal excitatory neurons. Targeting α2δ-1-associated NMDARs may therefore represent a promising therapeutic approach for HIV-associated chronic neuropathic pain.
Torrens WA, Olshefsky S, Yankaway RB
… +5 more, Ruiz M, Coudriet KG, Price MK, Otto S, Haigh SM
Neuroscience
· 2026 Aug · PMID 42225165
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BACKGROUND: Standard electroencephalography (EEG) electrode caps, designed for fast and consistent placement, are incompatible with curly-to-coiled hair textures because electrodes cannot reliably reach the scalp. This d...BACKGROUND: Standard electroencephalography (EEG) electrode caps, designed for fast and consistent placement, are incompatible with curly-to-coiled hair textures because electrodes cannot reliably reach the scalp. This disproportionately affects specific ethnic groups. NEW METHOD: We developed the Universal Electroencephalography Clip (UE-C) for data collection across hair types and styles without requiring braiding procedures. We tested auditory and visual responses to assess signal quality across scalp regions. 57 participants (37 straight-to-wavy; 20 curly-to-coiled hair) heard auditory clicks at 4 Hz and viewed contrast-reversing gratings at 4/6Hz during EEG recording with the UE-C and the EEG cap. Epoch retention after artifact rejection and Signal-to-Noise Ratios (SNR) were compared across methods using ANOVAs and percent signal gain. RESULTS: The UE-C retained more epochs at both visual (+10% curly-to-coiled; +12% straight-to-wavy) and auditory regions (+8% curly-to-coiled; -8% straight-to-wavy) relative to the cap. Visual 4-Hz SNR was enhanced (p = 0.01) with straight-to-wavy, not curly-to-coiled (p = 0.06). SNRs improved at visual sites (signal gain: +34%; curly-to-coiled; +30% straight to wavy). Negligible effects were observed at the auditory site, where the electrode-to-scalp problem is less likely. COMPARISON WITH EXISTING METHODS: At the visual electrode, the UE-C retained more data with improved signal quality over the cap, despite hair texture. Auditory-site data were comparable between methods. The UE-C performed similarly to the SEVO clip, without braiding requirements and accommodating various hairstyles. CONCLUSIONS: We demonstrated another example of the electrode-to-scalp problem and share findings that offer a step forward toward correcting the hair bias in EEG methodology.
Int J Neurosci
· 2026 Jun · PMID 42219377
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AIM: This study aimed to evaluate the clinical value of upper limb rehabilitation robot-assisted training in stroke patients. METHODS: A total of 101 stroke patients were assigned to either conventional rehabilitation pl...AIM: This study aimed to evaluate the clinical value of upper limb rehabilitation robot-assisted training in stroke patients. METHODS: A total of 101 stroke patients were assigned to either conventional rehabilitation plus robot-assisted upper limb training ( = 50) or conventional rehabilitation alone ( = 51). The Fugl-Meyer Assessment of the Upper Extremity (FMA-UE), Modified Ashworth Scale for Upper Extremity (MAS-UE), Action Research Arm Test (ARAT), Functional Independence Measure (FIM) and quality-of-life outcomes were assessed. Oxygenated haemoglobin (HbO) levels in the affected primary motor cortex (M1), premotor cortex (PMC) and supplementary motor area (SMA) were measured. RESULTS: After treatment, both groups showed improvements in FMA-UE, MAS-UE, ARAT and FIM scores, with no significant difference between the groups. Quality of life improved in both groups; however, the study group had significantly higher post-treatment scores in the environmental, physical, social and psychological domains than the control group ( = 0.000). After treatment, HbO levels in the affected M1, PMC and SMA increased in both groups, with the study group showing higher levels ( < 0.05). CONCLUSION: Upper limb rehabilitation robot-assisted training improved quality of life and cortical activation in stroke patients but showed no additional benefit in motor function compared with conventional rehabilitation.
Yuvaraj R, Manickam T, Pulliyasseri A
… +1 more, Ardra M
Neuroscience
· 2026 May · PMID 42217612
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Boredom is a cognitive-affective state characterized by low attention and arousal. Its importance has been widely recognized across multiple domains, including education, where it negatively affects performance and acade...Boredom is a cognitive-affective state characterized by low attention and arousal. Its importance has been widely recognized across multiple domains, including education, where it negatively affects performance and academic achievement. However, its underlying neural mechanisms remain poorly understood. In this study, changes in brain network structure during non-bored and bored conditions were analyzed using EEG and graph-theoretical measures. A sample of twenty-five university students watched an educational video intended to induce boredom while their brain activity was recorded with an EEG. Following preprocessing, functional brain networks (FBNs) were constructed for each participant using a pairwise nonlinear mutual information (MI) measure applied to segmented EEG data. The resulting undirected, weighted, fully connected networks were sparsified using the Minimum Connected Component (MCC) thresholding algorithm. The resulting thresholded FBNs were then analyzed using global network metrics, which were computed and compared at the individual level between the non-boredom and boredom states. The experimental results showed that changes in brain network topology persisted throughout the participant's boredom state, with lower edge density, average degree centrality, clustering coefficient, and global efficiency, together with higher characteristic path length. Consequently, boredom disrupts both clustering within small-scale regions and integration across large-scale brain areas due to attentional disengagement and inefficient transfer of information. The study findings contribute to affective neuroscience by identifying neural markers of boredom and suggesting the possibility of developing a personalized EEG-based boredom-aware system for educational contexts and other fields.
Neuroscience
· 2026 Aug · PMID 42217611
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Glyphosate (GLY) is the active ingredient in most herbicides, including off-the-shelf weed killers such as Roundup®. GLY crosses the blood-brain barrier, increases oxidative stress and genotoxicity, and impacts reproduct...Glyphosate (GLY) is the active ingredient in most herbicides, including off-the-shelf weed killers such as Roundup®. GLY crosses the blood-brain barrier, increases oxidative stress and genotoxicity, and impacts reproduction, but the extent of its effects remains unclear. Previous research reports conflicting evidence on sex-specific susceptibility to GLY's effects, and very few investigate the effects of a single, acute dose on learning, memory, and neuronal activation. In vitro studies have found GLY interferes with gene expression and is uniquely capable of inducing DNA double strand breaks (DSBs) compared to other herbicides. DSBs can induce expression of immediate early genes (IEGs), which are important for synaptic plasticity, learning, and memory. However, a clear connection between GLY, IEGs, and learning and memory has yet to be made. To explore this, we tested male and female wildtype mice in novel object recognition after they received an acute, oral dose of 0, 250, or 500 mg/kg of GLY and assessed hippocampal DSB and IEG levels. We hypothesized that a single dose of GLY would impair memory by disrupting IEG expression and would affect males more than females. We did not find robust evidence that GLY impaired memory, though females that received 500 mg/kg did not explore the novel object more than the familiar. Hippocampal DSBs were decreased following 500 mg/kg in both sexes, yet hippocampal IEG immunoreactivity was decreased in GLY-exposed males only, revealing a complex sex-dependent relationship. These data add to the literature that GLY is potentially detrimental, highlighting the need for further investigations.
Broniszeski A, Telfer A, Fortin T
… +3 more, Sun H, Abizaid A, Hayley S
Neuroscience
· 2026 May · PMID 42217610
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Preclinical animal models of eating disorders show a clear relationship between stress in the adolescent period and the development of dysfunctional coping strategies, including disordered eating. Much of this work, howe...Preclinical animal models of eating disorders show a clear relationship between stress in the adolescent period and the development of dysfunctional coping strategies, including disordered eating. Much of this work, however, has focused on male mice despite the fact that eating disorders are predominantly observed in women. To this end, we assessed the impact of social isolation and food deprivation in adolescent female mice upon feeding and other coping behaviors. We found that social isolation, together with food restriction, caused alterations in activity levels and feeding consistent with impulsive binging behaviour in adolescent female mice. Indeed, socially isolated mice that were food restricted (FR) exhibited signs of elevated feeding following exposure to a palatable food and upon reinstatement of ad libitum (AL) food chow. FR mice also showed elevated home-cage activity and together with social isolation, altered Y-maze performance. Finally, the adolescent stress regimen appeared to cause long lasting brain atrophy, as occurs in eating disorders, as reflected by reduced gross brain weight. Hence, social isolation, when combined with restricted feeding during adolescence in female mice results in a behavioral phenotype reminiscent of symptoms associated with some eating disorders, such as binge eating.
Neuroscience
· 2026 Aug · PMID 42217609
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The monosynaptic Ia afferent pathway provides direct and strong excitatory drive to spinal motoneurons (MNs), forming a critical substrate for reflex modulation, intermuscular coordination, and motor performance. Despite...The monosynaptic Ia afferent pathway provides direct and strong excitatory drive to spinal motoneurons (MNs), forming a critical substrate for reflex modulation, intermuscular coordination, and motor performance. Despite its central role in sensorimotor control, it has remained unclear how different forms of physical training reshape the Ia input to MNs. In this review, we summarize recent intracellular studies in rats revealing a pattern of MN-type specific plasticity. Whole‑body vibration and progressive weight‑lifting training, both characterized by the recruitment of high‑threshold motor units, produce robust potentiation of Ia excitatory postsynaptic potentials (EPSPs) in fast‑type MNs. In contrast, endurance treadmill running, which relies heavily on the recruitment of slow, fatigue‑resistant motor units, selectively strengthens Ia EPSPs in slow‑type MNs. These findings support a paradigm that Ia synaptic excitation is preferentially enhanced on the MNs most frequently and intensely recruited during a given training task. This selectivity provides mechanistic insight into how the spinal cord optimizes proprioceptive integration to support improvements in strength, motor coordination, and endurance, with important implications for training purposes and rehabilitation strategies.
Shahabinejad E, Kamali M, Shakoeizadeh A
… +7 more, Falakian Z, Foroughi Eghbal A, Alipour SM, Krywyj M, Sheehan JP, Alrashidi Q, Borghei-Razavi H
Int J Neurosci
· 2026 Jun · PMID 42217213
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BACKGROUND: Secretory meningioma (SM) is an uncommon variety of meningioma, representing about 1-3% of cases. Notwithstanding its benign classification, SM is frequently associated with excessive peritumoral brain edema...BACKGROUND: Secretory meningioma (SM) is an uncommon variety of meningioma, representing about 1-3% of cases. Notwithstanding its benign classification, SM is frequently associated with excessive peritumoral brain edema (PTBE), resulting in considerable morbidity. This study examines the epidemiology, clinical presentation, imaging characteristics, histological features, immuno-histochemical profile and genetic landscape of SM, along with management methods and results. MATERIALS AND METHODS: We performed a structured search in PubMed, Scopus, and Web of Science up up to October 2025 using keywords including "secretory meningioma" "meningioma", "peritumoral brain edema", and related terms. Original and review articles in English were included. Relevant data were extracted and narratively synthesized covering clinical, radiological, pathological, and genetic features. RESULTS: SM is defined by the presence of pseudopsammoma bodies, pronounced immunoreactivity for carcinoembryonic antigen (CEA) and epithelial membrane antigen (EMA), and a unique molecular profile featuring KLF4 K409Q and TRAF7 mutations. Radiologically, PTBE is characterized by fluid-attenuated inversion recovery (FLAIR) hyperintensity and increased apparent diffusion coefficient (ADC) values serves as critical diagnostic indicators. While surgical gross complete resection is the gold standard, significant postoperative tumor bed edema complicates perioperative treatment and may necessitate additional therapies. CONCLUSION: Identifying SM as a unique clinical entity is essential for diagnosis, prognosis and therapeutic approaches.
Int J Neurosci
· 2026 Jun · PMID 42216302
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BACKGROUND: Glioma is a primary tumor derived from central nervous system glial cells. RNA binding motif protein 25 (RBM25) has been implicated in glioma progression, yet its underlying molecular mechanism remains incomp...BACKGROUND: Glioma is a primary tumor derived from central nervous system glial cells. RNA binding motif protein 25 (RBM25) has been implicated in glioma progression, yet its underlying molecular mechanism remains incompletely understood. METHODS: In this study, glioma-related datasets were retrieved from the Proteomic Data Commons (PDC) and Gene Expression Omnibus (GEO) databases. Core glioma-associated targets were screened using machine learning algorithms. Protein expression was assessed by Western blot, while migration, and invasion, cell cycle and apoptosis were analyzed by Transwell assay and flow cytometry. Chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays were used to validate the interaction between transcription factors and genes. RESULTS: Proteomic analysis revealed distinct differences between glioma and control groups, with differentially expressed proteins mainly enriched in mitochondrial energy metabolism, synaptic function, and neurodegenerative disease pathways. Transcriptomic profiles also exhibited significant alterations, with RBM25 and HSPA8 showing consistent changes at both protein and RNA levels. Multiple machine learning models identified RBM25, NKTR, MAP2K6, TRAPPC3, and HSPA8 as key genes associated with glioma, with RBM25 and NKTR showing strong relevance in model-based feature selection. RBM25 was upregulated in glioma and linked to neuronal signaling pathways, whereas HSPA8 and TRAPPC3 were downregulated. RBM25 knockdown suppressed glioma cell proliferation, migration, and invasion, and induced cell cycle arrest and apoptosis. CONCLUSION: RBM25 contributes to glioma malignancy and may serve as a potential biomarker and therapeutic target for glioma.
In Alzheimer's disease (AD), endogenous tau undergoes a pathogenic transition to form paired helical filaments (PHFs), but the cellular mechanisms driving this process have been elusive. Here, we identify the neuron-spec...In Alzheimer's disease (AD), endogenous tau undergoes a pathogenic transition to form paired helical filaments (PHFs), but the cellular mechanisms driving this process have been elusive. Here, we identify the neuron-specific plasma membrane proteasome ('neuroproteasome') as a critical determinant of tau proteostasis. Selective inhibition of neuroproteasome function rapidly triggers the de novo formation of endogenous, sarkosyl-insoluble tau PHFs in primary neurons and mouse brain, which share key biochemical and ultrastructural features with PHFs from human AD brains. The APOE gene has three isoforms (E2, E3 and E4), with APOE4 being the largest genetic risk factor for AD. Neuroproteasome abundance at the plasma membrane is differentially modulated by ApoE isoforms (E2 > E3 > E4) and declines with age. ApoE4 neurons accumulate tau aggregates following modest neuroproteasome disruption, whereas ApoE2 neurons remain resistant. Our findings delineate a neuron-specific mechanism linking genetic and age-related risk factors to the formation of AD-relevant tau pathology, and position neuroproteasome function as a potential target to preserve proteostasis.