BACKGROUND: Parkinson\'s disease (PD), the most prevalent type of Parkinsonism, is a progressive neurological condition characterized by a range of motor and non-motor symptoms. The complicated etiology of PD is thought to involve a summation of aging, genetic predisposition, and environmental variables. However, the α-synuclein protein plays a significant role in the disease\'s pathophysiology.
METHODS: The UAS-α-Syn and Ddc-Gal4 strains were crossed to produce offspring referred to as PD flies. The entire population of flies was divided into five groups, each having about 100 flies and five replicates. The control group (w1118) and the PD group not receiving treatment were exposed to lauric acid (LA)/levodopa (LD)-free diet, while the PD groups that received treatments were fed with either a 250 mg/kg LA diet, a 250 mg/kg LD diet, or a combination of the two for 21 days. Longevity, geotaxis, and olfactory assays were performed in addition to other biochemical tests.
RESULTS: As a result of the overexpression of α-synuclein, the locomotive capacity, lifespan, and antioxidant status were all significantly (p < .05) reduced, and the apoptotic and neuroinflammatory activities were increased. Nevertheless, the majority of the treated flies improved significantly (p < .05).
CONCLUSIONS: LA, whether combined with LD or not, elicited a significant response in α-synuclein/dopa decarboxylase genetically modified Drosophila melanogaster Parkinsonism models.

Parkinsonism in rats induced by the pesticide rotenone is one of the most adequate models of Parkinson\'s disease (PD). Isatin (indole-2,3-dione) is an endogenous regulator found in mammals and humans and exhibiting a wide range of biological activities mediated by numerous isatin-binding proteins, including those associated with neurodegenerative pathology. A course of rotenone administration to rats caused behavioral impairments and changes in the profile and relative content of isatin-binding proteins in the brain. In this study, we have investigated the delayed neuroprotective effect of isatin (5 days after completion of the course of rotenone administration) on behavioral reactions and the relative content of isatin-binding proteins in the brain of rats with rotenone-induced experimental parkinsonism. Although during this period the rats retained locomotor dysfunction, the proteomic analysis data (profile of isatin-binding proteins in the brain and changes in their relative content) differed from the results obtained immediately after completion of the course of rotenone administration. Moreover, all isatin-binding proteins with altered relative content changed during this period are associated to varying degrees with neurodegeneration (many with Parkinson\'s and Alzheimer\'s diseases).

BACKGROUND: The cerebellar response has been studied for years with different models of alteration of other brain structures to understand its complex functioning and its relationship with the rest of the body. Studies in patients with Parkinson\'s disease (PD) showed that the cerebellar function is modified by deficit of the basal ganglia; which supports the hypothesis that both structures are related anatomically and functionally.
METHODS: In our study, the ventrolateral striatum (VLS) of the basal ganglia was altered by an electrolytic lesion, in order to produce a similar jaw frequency of jaw tremor movements presented in parkinsonism, thereafter we analyzed the effect of the lesion on the expression of multiunit activity (MUA) of the cerebellum.
RESULTS: We found cerebellar activation during mandibular movements and increment during oral jaw tremor movements. In addition, the amplitude of baseline MUA registered in animals with alteration of the VLS decreased with respect to the intact group.
CONCLUSIONS: Accordingly, we conclude that cerebellar changes in MUA may be due to a decrease in the cerebellar inflectional or as a possible compensatory function between cerebellum and basal ganglia.

UNASSIGNED: Parkinson\'s disease (PD) causes a decline in motor function, cognitive decline, and impacts the mental health of patients. Due to the high cost and side effects of conventional treatments, the medical community has begun to explore safer and more cost-effective alternative therapies. In this context, arts therapies have gained increasing attention as innovative treatments. This review plans to explore the role and potential of various arts therapies in the rehabilitation of PD patients by analyzing existing literature and case studies.
UNASSIGNED: This review comprehensively searched the literature in several databases, including PubMed, Embase, Cochrane Library, Web of Science, and China National Knowledge Infrastructure, to assess the effectiveness of different arts therapies in the rehabilitation of patients with PD.
UNASSIGNED: From 3440 articles screened, 16 met the inclusion criteria. These studies included a variety of therapies, including music, meditation, yoga, art, dance, theatre, video games and play therapy. These different types of arts therapies had a positive impact on the motor, psychological and cognitive rehabilitation of PD patients, respectively.
UNASSIGNED: The existing literature highlights the great potential of arts therapies in the rehabilitation of people with PD, further confirming the efficacy of arts therapies in enhancing the motor, psychological and cognitive rehabilitation process of people with PD. In addition, this review identifies research gaps in the use of color therapy in PD rehabilitation and highlights the need for further exploration of various arts therapies modalities.

Parkinson\'s disease (PD) is characterized by neuroinflammation, progressive loss of dopaminergic neurons, and accumulation of α-synuclein (α-Syn) into insoluble aggregates called Lewy pathology. The Line 61 α-Syn mouse is an established preclinical model of PD; Thy-1 is used to promote human α-Syn expression, and features of sporadic PD develop at 9-18 months of age. To accelerate the PD phenotypes, we injected sonicated human α-Syn preformed fibrils (PFFs) into the striatum, which produced phospho-Syn (p-α-Syn) inclusions in the substantia nigra pars compacta and significantly increased MHC Class II-positive immune cells. Additionally, there was enhanced infiltration and activation of innate and adaptive immune cells in the midbrain. We then used this new model, Line 61-PFF, to investigate the effect of inhibiting the JAK/STAT signaling pathway, which is critical for regulation of innate and adaptive immune responses. After administration of the JAK1/2 inhibitor AZD1480, immunofluorescence staining showed a significant decrease in p-α-Syn inclusions and MHC Class II expression. Flow cytometry showed reduced infiltration of CD4+ T-cells, CD8+ T-cells, CD19+ B-cells, dendritic cells, macrophages, and endogenous microglia into the midbrain. Importantly, single-cell RNA-Sequencing analysis of CD45+ cells from the midbrain identified 9 microglia clusters, 5 monocyte/macrophage (MM) clusters, and 5 T-cell (T) clusters, in which potentially pathogenic MM4 and T3 clusters were associated with neuroinflammatory responses in Line 61-PFF mice. AZD1480 treatment reduced cell numbers and cluster-specific expression of the antigen-presentation genes H2-Eb1, H2-Aa, H2-Ab1, and Cd74 in the MM4 cluster and proinflammatory genes such as Tnf, Il1b, C1qa, and C1qc in the T3 cluster. Together, these results indicate that inhibiting the JAK/STAT pathway suppresses the activation and infiltration of innate and adaptive cells, reducing neuroinflammation in the Line 61-PFF mouse model.

OBJECTIVE: There is no disease-modifying treatment of corticobasal syndrome (CBS) and progressive supranuclear palsy (PSP), 2 disorders characterized by their striking phenotypic, and, in CBS, pathologic heterogeneity. Seed amplification assays (SAAs) could enable the detection of neuropathologic processes, such as α-synuclein (αSyn) copathology, that affect the success of future disease-modifying treatment strategies. The primary objective was to assess possible αSyn copathology in CBS and PSP, as detected in CSF using an αSyn SAA (αSyn-SAA). Secondary objectives were to evaluate the association of αSyn-SAA positivity with other biomarkers including of Alzheimer disease (AD), and with clinical presentation. We hypothesized that αSyn-SAA positivity would be detectable in CBS and PSP and that it would be associated with AD biomarker positivity and β-amyloid (Aβ) 42 levels, neurodegeneration as assessed by neurofilament light chain (NfL) levels, and symptoms associated with synucleinopathies.
METHODS: This cross-sectional observational study included patients clinically diagnosed with CBS and PSP who underwent a lumbar puncture between 2012 and 2021 (Toronto Western Hospital, Canada). CSF was tested for αSyn-SAA positivity, AD biomarkers, and NfL levels. Clinical data were derived from medical records.
RESULTS: We tested the CSF of 40 patients with CBS (19 female patients, 65.9 ± 8.6 years) and 28 with PSP (13 female patients, 72.5 ± 8.7 years old), mostly White (n = 50) or Asian (n = 14). αSyn-SAA positivity was observed in 35.9% patients with CBS and 28.6% with PSP. In young-onset, but not late-onset patients, αSyn-SAA positivity and AD positivity were associated (odds ratio [OR] 8.8, 95% CI 1.2-82.6, p < 0.05). A multivariable linear regression analysis showed a significant interaction of αSyn-SAA status by age at onset on CSF Aβ42 levels (β = 0.3 ± 0.1, p < 0.05). Indeed, age at onset was positively related to Aβ42 levels only in αSyn-SAA-positive patients, as shown by slope comparison. A logistic regression analysis also suggested that REM sleep behavior disorder was associated with αSyn-SAA positivity (OR 60.2, 95% CI 5.2-1,965.8; p < 0.01).
CONCLUSIONS: We detected a frequency of αSyn-SAA positivity in CBS and PSP in line with pathologic studies, highlighting the usefulness of SAAs for in vivo detection of otherwise undetectable neuropathologic processes. Our results also suggest that AD status (specifically low Aβ42) and older age at onset may contribute to αSyn-SAA positivity. This opens new perspectives for the stratification of patients in clinical trials.

UNASSIGNED: Despite being the second most common type of neurodegeneration with brain iron accumulation, there is limited literature on PLA2G6-associated neurodegeneration (PLAN) within the Asian ethnicity, particularly in the Indian context.
UNASSIGNED: We conducted a retrospective observational study on patients with pathogenic/likely pathogenic PLA2G6 variants based on exome sequencing.
UNASSIGNED: We identified 26 patients (22 families, 15 males) of genetically-confirmed PLAN with a median age of 22.5 years and age at onset of 13.0 years, encompassing various subtypes: infantile neuroaxonal dystrophy (5/26;19.2%), atypical neuroaxonal dystrophy (3/26;11.5%), dystonia-parkinsonism (5/26;19.2%), dystonia-parkinsonism-myoclonus (n = 4, 15.38%), early-onset Parkinson\'s disease (2/26;7.7%), complex dystonia (2/26;7.7%), and complicated hereditary spastic paraparesis (cHSP; 5/26;19.2%). The common initial symptoms included walking difficulty (7/26;26.9%), developmental regression (6/26;23.1%), and slowness (4/26;15.4%). Dystonia (14/26;53.8%), followed by parkinsonism (11/26; 42.3%), was the most common motor symptom. Non-motor symptoms included cognitive decline (12/26;46.2%) and behavioral changes (6/26;23.1%). Neuroimaging revealed cerebellar atrophy in 23/26 (88.5%) patients and claval hypertrophy in 80% (4/5) of INAD patients. Levodopa responsiveness was noted in 12 of 14 patients with parkinsonism/dystonia who received levodopa, and dyskinesia was noted in 10/11 patients. Genetic analysis revealed a total of 19 unique variants in PLA2G6 gene, of which 11 were novel. Twelve patients harbored the c.2222G>A variant, which is predominantly seen in Asian subpopulations.
UNASSIGNED: The study introduces 26 new patients of PLAN and 12 patients associated with the c.2222G>A variant, potentially forming the most extensive single center series to date. It also expands the phenotypic, neuroimaging, and genotypic spectrum of PLAN.

暂无摘要。

Synucleins, including α-synuclein (α-syn), β-syn, and γ-syn, have been implicated in various synucleinopathies, notably Parkinson\'s disease (PD), which has generated increased interest in understanding their roles. Although α-syn and β-syn have contrasting neuropathological consequences, the precise role of γ-syn remains unclear. This study validated non-motor symptoms, specifically anxiety-like behavior, along with the degradation of dopaminergic (DAergic) neurons in the nigrostriatal system and DAergic neurites in the prefrontal cortex and hippocampus of rats infused with striatal 6-hydroxydopamine (6-OHDA). Our study further investigated the alterations in γ-syn expression levels in the prefrontal cortices and hippocampi of these 6-OHDA-treated rats, aiming to establish foundational insights into the neuropathophysiology of DA depletion, a central feature of PD. Our findings revealed a significant increase in the expression of γ-syn mRNA and protein in these brain regions, in contrast to unaltered α- and β-syn expression levels. This suggests a distinct role of γ-syn within the neurobiological milieu under conditions of DA deficiency. Overall, our data shed light on the neurobiological changes observed in the hemiparkinsonian rat model induced with 6-OHDA, underscoring the potential significance of γ-syn in PD pathology.

Parkinson\'s disease (PD) involves the degeneration of dopaminergic neurons in the substantia nigra (SNpc) and manifests with both classic and non-classic motor symptoms, including respiratory failure. Our study aims to investigate the involvement of the commissural and intermediate nucleus of the solitary tract (cNTS and iNTS) in the attenuated respiratory response to hypoxia in PD. Using a PD rat model induced by bilateral injection of 6-hydroxydopamine (6-OHDA) into the striatum of male Wistar rats, we explored potential alterations in the population of Phox2b neurons or hypoxia-activated neurons in the NTS projecting to the retrotrapezoid nucleus (RTN). Additionally, we explored neuronal connectivity between SNpc and cNTS. Projections pathways were assessed using unilateral injection of the retrograde tracer Fluorogold (FG) in the cNTS and RTN. Neuronal activation was evaluated by analyzing fos expression in rats exposed to hypoxia. In the PD model, the ventilatory response, measured through whole-body plethysmography, was impaired at both baseline and in response to hypoxia. A reduction in Phox2b-expressing neurons or hypoxia-activated neurons projecting to the RTN was observed. Additionally, we identified an indirect pathway linking the SNpc and cNTS, which passes through the periaqueductal gray (PAG). In conclusion, our findings suggest impairment in the SNpc-PAG-cNTS pathway in the PD model, explaining the loss of Phox2b-expressing neurons or hypoxia-activated neurons in the cNTS and subsequent respiratory impairment during hypoxic stimulation. We propose that the reduced population of Phox2b-expressing neurons in the NTS may include the same neurons activated by hypoxia and projecting to the RTN.