RNA splicing is an essential cellular process in which a series of protein-nucleic acid complexes cut and splice the products of gene transcription to generate mature RNA， and it plays an important role in maintaining the normal life activities of cells. Extensive studies have shown that proteins and nucleic acids associated with RNA splicing undergo the pathological changes such as aggregation in neurodegenerative diseases， and inadequate RNA splicing is observed in lesions. Genetic alterations within RNA splicing-related genes can cause neurodegenerative diseases. All these findings suggest that abnormalities in RNA splicing pathways may play a significant role in the pathogenesis of neurodegenerative diseases. This article reviews the research advances in the alterations of RNA splicing in common neurodegenerative diseases in terms of histopathology， biochemistry， and genetics， as well as related cell biology and animal models， in order to clarify their role in the pathogenesis of neurodegenerative diseases.
Alzheimer Disease ; Parkinson Disease

The aim of this study is to investigate the protective effect of idebenone (IDE) combined with borneol (BO) against Parkinson's disease (PD). In this study, wild-type AB zebrafish and transgenic Tg ( vmat2: GFP) zebrafish with green fluorescence labeled dopamine neurons were used to establish the PD model with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP). Following drug treatment, the behavioral performance and dopamine neuron morphology of zebrafish were evaluated, and regulation of dopamine signaling pathway-related genes was determined using RT-qPCR. The results showed that IDE combined with BO improved the behavioral disorders of zebrafish such as bradykinesia and shortening movement distance, also effectively reversed the damage of MPTP-induced dopaminergic neurons. At the same time, the expression of dopamine synthesis and transportation-related genes was up-regulated, and the normal function of the signal transduction pathway was restored. The combination showed a better therapeutic effect compared to the IDE monotherapy group. This study reveals the protective mechanism of IDE combined with BO on the central nervous system for the first time, which provides an important experimental basis and theoretical reference for clinical combination strategy in PD treatment.
Animals ; Zebrafish ; Signal Transduction/drug effects* ; Animals, Genetically Modified ; Dopamine/metabolism* ; Neuroprotective Agents/pharmacology* ; Disease Models, Animal ; Camphanes/pharmacology* ; Ubiquinone/pharmacology* ; Parkinson Disease/drug therapy* ; Dopaminergic Neurons/metabolism*

Depression (Dep) is one of the most common concomitant symptoms of Parkinson's disease (PD), but there is a lack of detailed pathologic evidence for the occurrence of PD-Dep. Currently, the management of symptoms from both conditions using conventional pharmacological interventions remains a formidable task. In this study, we found impaired activation of extracellular signal-related kinase (ERK), reduced levels of transcription and translation, and decreased expression of brain-derived neurotrophic factor (BDNF) in the medial prefrontal cortex (mPFC) of PD-Dep rats. We demonstrated that the abnormal phosphorylation of α-synuclein (pS129) induced tropomyosin-related kinase receptor type B (TrkB) retention at the neuronal cell membrane, leading to BDNF/TrkB signaling dysfunction. We chose SEW2871 as an ameliorator to upregulate ERK phosphorylation. The results showed that PD-Dep rats exhibited improvement in behavioral manifestations of PD and depression. In addition, a reduction in pS129 was accompanied by a restoration of the function of the BDNF/ERK signaling loop in the mPFC of PD-Dep rats.
Animals ; Brain-Derived Neurotrophic Factor/metabolism* ; alpha-Synuclein/metabolism* ; Male ; Prefrontal Cortex/drug effects* ; Rats, Sprague-Dawley ; Depression/metabolism* ; MAP Kinase Signaling System/drug effects* ; Rats ; Parkinson Disease/metabolism* ; Receptor, trkB/metabolism* ; Phosphorylation ; Disease Models, Animal ; Signal Transduction

The ventral anterior (VA) nucleus of the thalamus is a major target of the basal ganglia and is closely associated with the pathogenesis of Parkinson's disease (PD). Notably, the VA receives direct innervation from the hypothalamic histaminergic system. However, its role in PD remains unknown. Here, we assessed the contribution of histamine to VA neuronal activity and PD motor deficits. Functional magnetic resonance imaging showed reduced VA activity in PD patients. Optogenetic activation of VA neurons or histaminergic afferents significantly alleviated motor deficits in 6-OHDA-induced PD rats. Furthermore, histamine excited VA neurons via H1 and H2 receptors and their coupled hyperpolarization-activated cyclic nucleotide-gated channels, inward-rectifier K⁺ channels, or Ca²⁺-activated K⁺ channels. These results demonstrate that histaminergic afferents actively compensate for Parkinsonian motor deficits by biasing VA activity. These findings suggest that targeting VA histamine receptors and downstream ion channels may be a potential therapeutic strategy for PD motor dysfunction.
Animals ; Histamine/metabolism* ; Male ; Oxidopamine/toxicity* ; Rats ; Ventral Thalamic Nuclei/physiopathology* ; Rats, Sprague-Dawley ; Disease Models, Animal ; Parkinson Disease/metabolism* ; Neurons/physiology* ; Humans ; Optogenetics

Parkinson's disease (PD), a chronic and common neurodegenerative disease, is characterized by the progressive loss of dopaminergic neurons in the dense part of the substantia nigra and abnormal aggregation of alpha-synuclein. Type 2 diabetes mellitus (T2DM) is a metabolic disease characterized by chronic insulin resistance and deficiency in insulin secretion. Extensive evidence has confirmed shared pathogenic mechanisms underlying PD and T2DM, such as oxidative stress caused by insulin resistance, mitochondrial dysfunction, inflammation, and disorders of energy metabolism. Conventional drugs for treating T2DM, such as metformin and glucagon-like peptide-1 receptor agonists, affect nerve repair. Even drugs for treating PD, such as levodopa, can affect insulin secretion. This review summarizes the relationship between PD and T2DM and related therapeutic drugs from the perspective of insulin signaling pathways in the brain.
Humans ; Parkinson Disease/drug therapy* ; Diabetes Mellitus, Type 2/pathology* ; Signal Transduction/physiology* ; Receptor, Insulin/metabolism* ; Animals ; Insulin Resistance/physiology* ; Insulin/metabolism*

Pain is one of the common non-motor symptoms in patients with Parkinson disease and is characterized by early onset， a high incidence rate， and diverse types of discomfort， which seriously affects the quality of life of patients. Based on the related concepts of pain in Parkinson disease and the current status of research in China， this article reviews the commonly used non-pharmaceutical interventions for alleviating pain in patients and their mechanisms， in order to provide a basis for developing pain management regimens.
Parkinson Disease ; Pain

Objective To investigate the characteristics of tremor in Parkinson disease （PD）， essential tremor （ET）， and neuronal intranuclear inclusion disease （NIID）. Methods The surface electromyography （sEMG） data of both upper limbs were collected from 73 patients with tremor （30 patients in PD group， 23 in ET group， and 20 in NIID group）， and the a power spectral analysis was used to investigate frequency characteristics. A one-way analysis of variance and the chi-square test were used for comparison of electrophysiological parameters on sEMG between the three groups. Results The ET group had a higher tremor frequency than the PD group （F=41.86， P<0.01）， while the PD group had a higher tremor frequency than the NIID group in resting state （F=41.86， P=0.002） and in postural state （F=41.86， P=0.011）. The PD group had a higher proportion of patients with alternating contractions than the NIID group in resting state （χ2=5.70， P=0.017） and in postural state （χ2=7.24， P=0.007）， as well as a higher proportion of such patients than the ET group （χ2=9.67， P=0.002）. The PD group also had a higher proportion of patients with harmonic resonances than the NIID group in resting state （χ2=4.64， P=0.031） and in postural state （χ2=7.73， P=0.005）， as well as a higher proportion of such patients than the ET group （χ2=6.52， P=0.011）. Conclusion The highest tremor frequency is observed in ET， while the lowest tremor frequency is observed in NIID； patients with PD have a higher proportion of individuals with alternating contractions or harmonic resonances than patients with NIID and ET.
Parkinson Disease ; Tremor

Objective To investigate the state of anxiety and depression in patients with Parkinson disease due to high-altitude exposure in Tibet， China and its impact on quality of life. Methods A total of 93 patients with Parkinson disease who attended Tibet Autonomous Region People’s Hospital from February 2023 to November 2024 were enrolled， and basic information and assessment scales were collected. The Unified Parkinson’s Disease Rating Scale Part Ⅲ （UPDRS-Ⅲ） and Hoehn-Yahr （H-Y） stage were used to evaluate disease severity； Parkinson’s Disease Quality of Life Questionnaire （PDQ-39） was used to evaluate the quality of life of patients； the diagnostic criteria for depression and anxiety in Parkinson disease were used for the diagnosis of depression and anxiety in patients with Parkinson disease； Hamilton Depression Scale （HAMD） and Hamilton Anxiety Scale （HAMA） were used to assess the severity of depression and anxiety. Results Among the 93 patients with Parkinson disease， the prevalence rates of depression and anxiety were 59.1% and 44.1%， respectively. There were significant differences between the depression group and the non-depression group in the somatization， despair， cognitive impairment， block factor， and day-night changes of anxiety， but there were no significant differences in sleep disorders and body weight between the two groups. The depression group had significantly higher PDQ-39 scores than the non-depression group， and the anxiety group had significantly higher PDQ-39 scores than the non-anxiety group. Depressive state was negatively correlated with folate and was positively correlated with blood homocysteine. Anxiety state was positively correlated with H-Y stage and UPDRS Ⅲ score. Conclusion There are relatively high prevalence rates of depression and anxiety in patients with Parkinson disease in Tibetan plateau area， which significantly affects the quality of life of patients.
Parkinson Disease ; Depression ; Anxiety

Objective To investigate the clinical features of dyskinesia and related risk factors in female patients with Parkinson disease （PD）. Methods A cross-sectional study was conducted among the female patients who met the diagnostic criteria for PD at the outpatient service of PD in Aerospace Center Hospital， and demographic data and clinical data were collected and compared between groups， including levodopa equivalent daily dose （LEDD）， Unified Parkinson’s Disease Rating Scale-Ⅲ（UPDRS-Ⅲ）， UPDRS-Ⅳ， scores of non-motor symptoms （cognition and depression）， presence or absence of dyskinesia， and single levodopa dose （LD） during the onset of dyskinesia. A binary logistic regression analysis was used to investigate the influencing factors for dyskinesia in female patients with PD. Results A total of 146 female PD patients were enrolled， among whom 30 patients had dyskinesia， with an incidence rate of 20.5%. Compared with the non-dyskinesia group in terms of clinical features， the dyskinesia group had a significantly younger age of onset [（54.3±12.5） years vs （62.7±10.0） years， P<0.001]， a significantly longer disease duration [（9.9±3.7） years vs （4.5±3.7） years， P<0.001]， a significantly higher severity of disease [H-Y stage： （2.65±0.58） vs （2.35±0.83）， P=0.03]， a significantly longer duration of LD administration [（7.5±3.2） years vs （3.2±2.6） years， P<0.001]， a significantly higher LEDD [（703.2±203.9） mg vs （442.1±226.3） mg， P<0.001]， and significantly lower body weight [（54.1±8.2） kg vs （60.0±8.7） kg， P=0.001] and BMI [（20.9±3.1） kg/m2 vs （23.4±3.1） kg/m2， P<0.001]. The multivariate logistic regression analysis showed that high BMI （OR=0.770， P=0.005） was a protective factor against dyskinesia in female PD patients， while long disease duration （OR=1.304， P=0.001） and high LEDD （OR=1.003， P=0.012） were risk factors for dyskinesia. Conclusion There is a relatively high incidence rate of dyskinesia in female PD patients， which should be taken seriously in clinical practice， and high BMI is a protective factor， while long disease duration and high LEDD are risk factors for dyskinesia in female PD patients.
Parkinson Disease ; Dyskinesias ; Levodopa

Objective To investigate the association between depression and autonomic nervous function in Parkinson disease （PD）， and to provide a basis for clinical treatment. Methods Clinical and neurocirculation data were collected from 168 PD patients who attended Department of Neurology， The Second Affiliated Hospital of Hainan Medical College， from July 2022 to July 2023， and according to the score of Beck Depression Inventory， the patients were divided into depression in PD （dPD） group with 57 patients and non-dPD （nPD） group with 111 patients. General clinical data were collected from all patients. The supine-to-standing TCD test was performed for all patients to record systolic blood pressure （SBP）， diastolic blood pressure （DBP）， heart rate （HR）， and the mean velocity （Vm）， pulsatility index （PI）， and resistance index （RI） of the middle cerebral artery （MCA） at 1， 3， and 5 minutes in both the supine and standing positions. A network was constructed for depression symptoms in PD. Results In the network of non-motor symptoms in PD， depression showed the highest centrality and the strongest predictability and was strongly correlated with sleep/fatigue and mood/cognition， with a strength centrality stability coefficient （CS strength） of 0.440. Compared with the nPD group， the dPD group had significantly lower supine HR， ∆HR， Vm in the standing position， and ∆Vm%， a significantly greater ∆DBP， and a significantly higher proportion of patients with dizziness with orthostatic hypotension or orthostatic cerebral hypoperfusion （P<0.05）. Depression was positively correlated with ∆SBP， ∆DBP， Vm in the supine position， and RI in the standing position， and it was negatively correlated with ∆HR， DBP in the supine position， HR in the supine position， and ∆PI （CS strength=0.375 and 0.222）. Conclusion Impairment of cardiovascular and cerebral autonomic nervous function might be involved in the pathogenesis of depression in PD， and intervention of depression can help improve the overall non-motor symptoms of PD， with sleep， fatigue， and cognition as the effective targets for improving depression in PD.
Parkinson Disease ; Depression