Parkinson's disease (PD) and related familial Parkinsonism are defined by motor dysfunction, but the specific upstream molecular causes of these clinical symptoms can vary widely. We hypothesize that these causes converge onto a limited number of core cellular pathways. To investigate this, we created a collection of 24 genetically well-controlled Drosophila models of familial forms of PD and related mono-genic forms of Parkinsonism. Using unbiased behavioral screening and machine learning we identify clusters of mutants that converge on (1) mitochondrial function; (2) retromer/vesicle trafficking and proteostasis/autophagy. Genes within each cluster have a similar genetic interaction profile and compounds that target specific molecular pathways ameliorate dopaminergic neuron dysfunction in a cluster-specific manner. Together, our data indicate that familial PD and related forms of Parkinsonism may fall into two broad functional groups, and may inform further work toward targeted biomarker discovery and therapeutic development.

EAE models of neuropathic pain in multiple sclerosis do not require pertussis toxin.

Machine learning in stroke and its sequelae: a narrative review of clinical applications and emerging trends.

A novel brainstem-targeted G51D α-synuclein fibril-injected mouse model exhibits sequential emergence of sleep and motor dysfunction.

Exploring potential biomarkers of NETosis-Related genes in spinal cord injury through machine learning and multi-omics analysis.

Neuroprotective effects of Bifidobacterium animalis HN019 and Lactobacillus acidophilus NCFM in MPTP-induced Parkinson's disease mice.

Parkinson's disease (PD) is a neurodegenerative syndrome with diverse biological drivers, where gait and balance dysfunction remain among the most disabling and least understood symptoms. Bassoon (BSN), a presynaptic active-zone organizer, has been implicated in various parkinsonian disorders. Here, we report the impact of BSN mutations on motor symptoms, especially gait-related symptoms, in PD patients. Our study included 110 patients carrying BSN mutations in a cohort of 668 South Asian early-onset PD (age of onset < 50 years). Clinical motor features were compared between variant carriers and noncarriers. Computational tools (CADD, PolyPhen-2, I-Mutant2.0 and ConSurf) predicted deleteriousness of individual mutations, whereas GeneMANIA and STRING speculated Bassoon's functional interactions. Subjects carrying BSN variants exhibited significantly increased burden of motor-related symptoms (p = 0.036). Freezing of gait (FOG) and shuffling gait (SG) were significantly more prevalent in BSN mutation carriers (p = 0.03). Presence of BSN mutation correlated with an increased disease stage, an effect driven by FOG and SG (p = 0.012). Rare BSN mutations (MAF < 0.1%) clustered in the Bassoon C-terminal region (aa 3500-3800), at a threefold frequency than expected (p < 0.01), implying a hotspot. In silico analysis identified seven likely pathogenic variants (P171L, A852T, P988A, R1015H, R2561H, R3400W and L3561P). Predictive analyses implicated BSN in axonal transport, presynaptic proteostasis and neurotransmitter release in dopaminergic/cholinergic neurons. Our findings put forth BSN mutations as a potential genetic risk factor for PD-related motor and gait dysfunction, warranting further research in this respect.

Clinical effect and contributing factors of acupuncture for limb motor dysfunction after ischemic stroke: A systematic review and exploratory network meta-analysis.

Multi-omics study identifies diagnostic metabolic signatures of early Parkinson's disease associated with dysregulated glutathione and TCA cycle metabolism.

Fine hand motor dysfunction in a girl with epileptic encephalopathy with spike-and-wave activation in sleep (EE-SWAS): A case report

Huntington's disease (HD) is a devastating, autosomal dominant neurodegenerative disorder characterized by progressive motor dysfunction, cognitive decline, and psychiatric disturbances. Among the major pathological hallmarks of HD are mutant huntingtin aggregation, white matter loss and reactive astrogliosis, which together contribute to neuronal dysfunction and death, particularly in the striatum and cortex. Recent studies in HD mouse models have identified a specialized astrocyte subtype that clusters around white matter bundles originating from the secondary cortex and passing through the striatum. While the functional role of these astrocytes remains unclear, they express Glial Fibrillary Acidic Protein (GFAP), a marker typically associated with both fibrous and reactive astrocytes. The discovery of this white matter-associated astrocyte subtype, along with other astrocytic subtypes differing between grey and white matter, underscores the complexity of glial responses in HD. Accurate identification and interpretation of these glial populations are crucial for understanding disease mechanisms and progression. Given the overlapping expression profiles of commonly used astrocyte markers like GFAP, the careful selection and application of both astrocyte and white matter markers in histopathological analyses are essential to advance our understanding of how glial cells contribute to HD pathology. In this review we discuss different histopathological approaches to assess the roles of glia in HD, emphasizing the need for standardized approaches and critical evaluation of marker specificity.

Parkinson's disease (PD) is a common neurodegenerative disorder with a complex pathogenesis. 2,3,5,4'-Tetrahydroxy stilbene-2-O-β-D-glucoside (TSG) is one of the main active components of Polygonum multiflorum Thunb., which has therapeutic effects in various neurodegenerative diseases. The aim of this study was to explore the influence of TSG on the PD process. The PD mouse model was constructed via the use of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). The PD process was evaluated via behavioral tests, HE staining, immunohistochemistry, and immunofluorescence. The levels of related proteins and inflammatory factors were detected via western blotting and ELISA. The effect of TSG on the intestinal flora of MPTP-induced PD mice was evaluated through 16S rDNA sequencing. TSG intervention can significantly alleviate motor dysfunction in PD mice, increase the number of TH-positive neurons in the substantia nigra, inhibit the accumulation of α-syn and glial cell activation, reduce the expression of the tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-6, iNOS, and COX2 proteins in the substantia nigra and colon, inhibit neuroinflammation and intestinal inflammation, decrease the levels of LPS, LBP, TNF-α, IL-1β, and IL-6 in the serum, suppress systemic inflammation, reduce damage to the blood-brain barrier (BBB) and intestinal barrier in PD mice, and restore species diversity and abundance of the intestinal flora in PD mice to a certain extent. TSG can improve motor coordination ability, systemic and neuroinflammatory levels, BBB injury, intestinal barrier injury, and the intestinal flora composition of PD mice, suggesting that TSG has a protective effect on MPTP-induced PD mice.

A review of treatment methods for movement disorders.

Cognitive and Motor Dysfunction in STXBP1 R406H Mice.

Background: Bulbar dysfunction is a major complication of amyotrophic lateral sclerosis (ALS). This study aimed to develop and validate a simple, smartphone-based task for the objective assessment of tongue movements and to examine their association with clinical variables. Methods: 37 ALS patients and 20 age- and sex-matched controls performed a tongue lateralization task, recorded with a smartphone. A deep-learning U-Net++-based model was used for segmentation and feature extraction. The frequency and maximum amplitude of tongue movements were quantified. Clinical measures included the ALS Functional Rating Scale-revised (ALSFRS-r) bulbar sub-scores, tongue fasciculations, jaw jerk, and tongue “spasticity”. Between-group differences and associations between tongue metrics and clinical features were assessed. Results: The U-Net++-based model achieved robust segmentation performance. Patients showed lower tongue movement frequency than controls (0.14 vs. 0.40, t = −9.58, p &lt; 0.001). Normalized frequency was associated with dysarthria (t = −3.13, p = 0.003) but not dysphagia (t = −1.05, p = 0.30). Normalized frequency (t = 2.77, p = 0.009) and tongue “spasticity” (t = −2.57, p = 0.015) were both associated with speech performance in a multiple-regression model (R = 0.51, adjusted R2 = 0.43). Conclusions: Our method provides an objective, minimally invasive measure of bulbar function in ALS, which correlates with clinical ratings and may detect subtle impairments not captured by standard assessments. This approach offers a promising tool for remote monitoring and may support more effective disease management.

While the level of α-synuclein oligomers (α-SOs) in the CSF of patients with Parkinson's disease (PD) is consistently increased, its pathogenic role in PD remains poorly understood. This study focuses on the role of CSF-derived α-SOs in PD pathology. We demonstrated that CSF-derived α-synuclein enters the brain via perivascular spaces, which was more abundant in the olfactory bulb (OB) than in the substantia nigra (SN). We also found that neuroinflammation was more pronounced in the OB than in the SN following α-SOs injection. α-SOs-treated mice exhibited an early and persistent loss of dopaminergic (DA) neurons in the OB, along with olfactory deficit. Conversely, DA neuron loss in the SN occurred later and was associated with motor dysfunction. Furthermore, reducing α-SOs dose alleviated OB pathology. These findings suggest that perivascular spread of CSF-derived α-SOs induces region-specific PD-like pathology, indicating that removing CSF-derived α-SOs could slow PD progression.

Background Lower limb motor dysfunction is a common sequela of stroke that significantly impacts patients' walking safety and independence in daily living. Although brain-computer interface (BCI) technology has demonstrated efficacy in upper limb rehabilitation, its effects on lower limb recovery have not yet been systematically evaluated. Methods A systematic literature search was conducted across seven databases (PubMed, Web of Science, Embase, China National Knowledge Infrastructure, SinoMed, VIP Database, and Wanfang Data.) to identify studies investigating BCI for post-stroke lower limb dysfunction, encompassing records published up to September 2025. All statistical analyses were performed using Review Manager software (version 5.4.1). Results Thirteen studies involving 582 participants were included. BCI training significantly improved the scores of Fugl-Meyer Assessment for Lower Extremity (FMA-LE, MD = 2.67, 95%CI: 2.31–3.03, P &amp;lt; 0.00001, I 2 = 0%), Berg Balance Scale (BBS, MD = 7.04, 95%CI: 3.14–10.94, P = 0.0004), and Modified Barthel Index (MBI, MD = 6.72, 95%CI: 1.74–11.69, P = 0.008). Furthermore, a single study reported significant improvement in functional mobility measured by the Timed Up and Go Test (TUGT). Subgroup analysis for activities of daily living MBI showed that a cumulative training time of ≥ 500 min was associated with greater improvement. Conclusion BCI-based training is an effective approach for improving lower limb recovery after stroke, demonstrating benefits in motor function, balance, and functional mobility. While evidence for certain outcomes remains limited, the dose-dependent effect on daily living activities underscores the importance of sufficient training duration. Future research should validate these findings and clarify effects across a broader range of functional measures. Systematic review registration https://www.crd.york.ac.uk/PROSPERO/view/CRD420251150558 , identifier: CRD420251150558.

IntroductionIsolated cervical dystonia (ICD) is the most common focal dystonia, characterized by involuntary neck muscle contractions leading to abnormal head postures and nonmotor symptoms such as anxiety. Although structural and functional brain alterations have been reported, findings remain inconsistent, and the neurobiological mechanisms underlying motor and nonmotor symptoms remain incompletely understood.MethodsThirty-five ICD patients and twenty-eight matched healthy controls underwent structural MRI and resting-state fMRI. Voxel-based morphometry was used to assess gray matter volume (GMV) differences. Seed-based resting-state functional connectivity (rsFC) analyses were performed using regions with significant structural alterations. Partial correlation and mediation analyses examined associations among brain measures, motor severity, and mood symptoms.ResultsICD patients showed reduced GMV in the left paracentral lobule (PCL) and right middle temporal gyrus (MTG). The left PCL exhibited altered connectivity with prefrontal, temporal, and thalamic regions, indicating disruption of cerebello-thalamo-cortical pathways. The right MTG showed decreased connectivity with the left temporal pole and increased connectivity with the right middle frontal gyrus, suggesting compensatory mechanisms for cognitive processing. GMV reduction in the left PCL significantly mediated the relationship between ICD status and anxiety symptoms.DiscussionThese findings support ICD as a network disorder involving both motor and cognitive-affective circuits. Structural alterations in the PCL and MTG and their connectivity patterns may underlie motor dysfunction and nonmotor symptoms such as anxiety. Multimodal neuroimaging biomarkers may help guide targeted therapeutic interventions and improve clinical outcomes in ICD.

Utilizing non-human primates to study the role of human Tau and its related pathologies is logical and important due to their closer similarity to human brain structure and function. In our earlier research, we generated a transgenic cynomolgus monkey model expressing Tau (P301L) through lentiviral infection of monkey embryos. These monkeys exhibited age-dependent neurodegeneration and motor dysfunction. Single-nucleus RNA sequencing (snRNA-seq) is a powerful and promising technique for elucidating the cellular complexity and pathology across different tissues. However, single-cell data from non-human primate models of Tau pathology are currently nonexistent. In this study, we performed snRNA-seq on the hippocampus, striatum, and spinal cord of Tau (P301L) monkey, providing the first snRNA-seq atlas of multiple tissue regions in a non-human primate model that simulates human tauopathies. This will offer crucial data references for cross-species single-cell level studies of tau and its related pathologies.

Hypomorphic variants in the SEL1L-HRD1 ER-associated degradation (ERAD) complex have been linked to severe neurological syndromes in children, including neurodevelopmental delay, intellectual disability, motor dysfunction, and early death. Despite this association, its physiological importance and underlying mechanisms in neurons remain poorly understood. Here, we show that neuronal SEL1L-HRD1 ERAD is essential for maintaining one-carbon metabolism, motor function, and overall viability. Neuron-specific deletion of Sel1L in mice (Sel1LSynCre) resulted in growth retardation, severe motor impairments, and early mortality by 9 weeks of age-mirroring core clinical features observed in affected patients-despite preserved neuronal numbers and only modest ER stress. Multi-omics analyses, including single-nucleus RNA sequencing and metabolomics, revealed significant dysregulation of one-carbon metabolism in ERAD-deficient brains. This included activation of the serine, folate, and methionine pathways, accompanied by elevated levels of S-adenosylmethionine and related metabolites, likely resulted from induction of the integrated stress response (ISR). Together, these findings uncover a previously unappreciated role for neuronal SEL1L-HRD1 ERAD in coordinating ER protein quality control with metabolic adaptation, providing new insight into the molecular basis of ERAD-related neurodevelopmental disease.