Resting-State Functional MRI Regional Homogeneity Correlates With Motor Scores in Parkinson's Disease.

Background And Purpose: This study investigated the neural mechanisms underlying Parkinson's disease (PD) subtypes-tremor dominant (TD) and postural instability gait difficulty (PIGD)-by analyzing regional homogeneity (ReHo) values from resting-state functional MRI.

Methods: Fifty-nine PD patients (29 TD patients, 30 PIGD patients) and 30 healthy controls (HCs) were enrolled. ReHo values were analyzed via analysis of variance and a two-sample t-test, with age and sex as covariates.

LncRNA Tug1 Regulates Post-Stroke Microglial Pyroptosis via PINK1/Parkin-Mediated Mitophagy.

Microglia, the central nervous system's primary immune cells, play a key role in the progression of cerebral ischemic stroke, particularly through their involvement in pyroptosis. The long non-coding RNA taurine up-regulated gene 1 (Tug1) is elevated during ischemic stroke and is critical in driving post-stroke neuroinflammation. However, the underlying molecular mechanisms remain unclear.

α-Synuclein seeding amplification assays for diagnosing synucleinopathies: an innovative tool in clinical implementation.

The spectrum of synucleinopathies, including Parkinson's disease (PD), multiple system atrophy (MSA), and dementia with Lewy bodies (DLB), is characterized by α-synuclein (αSyn) pathology, which serves as the definitive diagnostic marker. However, current diagnostic methods primarily rely on motor symptoms that manifest years after the initial neuropathological changes, thereby delaying potential treatment. The symptomatic overlap between PD and MSA further complicates the diagnosis, highlighting the need for precise and differential diagnostic methods for these overlapping neurodegenerative diseases.

Corrigendum: Lipid profiles in the cerebrospinal fluid of rats with 6-hydroxydopamine-induced lesions as a model of Parkinson's disease.

[This corrects the article DOI: 10.3389/fnagi.2022.

STAT3 Inhibitor Increases α-Synuclein in PFF-Treated Astroglia Cells by Dysregulating Autophagy and Potentially Affects Exosome Biogenesis.

Astrocytes are the most abundant cells in the brain and show neuroprotective function in CNS and reactive astrocytes are characteristic in neurodegenerative diseases. The JAK2-STAT3 pathway plays a crucial role in the process of astrocyte activation. However, as a hallmark of Parkinson's disease, the change in α-syn under the influence of STAT3 inhibitor and the underlying cellular mechanisms remain elusive.

Optimal Preservation of PFFs in Glycerol Enhances Suitability for Modeling Parkinson's Disease.

Injecting α-synuclein pre-formed fibrils (αSyn PFFs) into various tissues and organs involves converting monomeric αSyn into a fibrillar form, inducing extensive αSyn pathology that effectively models Parkinson's disease (PD). However, the distinct physicochemical properties of αSyn amyloid fibrils can potentially reduce their seeding activity, especially during storage. In this study, it is demonstrated that αSyn PFFs exhibit significant sensitivity to low temperatures, with notable denaturation occurring between -20 and 4 °C, and gradual disassembly persisted even under storage conditions at -80 °C.

RAB12-LRRK2 complex suppresses primary ciliogenesis and regulates centrosome homeostasis in astrocytes.

The leucine-rich repeat kinase 2 (LRRK2) phosphorylates a subset of RAB GTPases, and their phosphorylation levels are elevated by Parkinson's disease (PD)-linked mutations of LRRK2. However, the precise function of the LRRK2-regulated RAB GTPase in the brain remains to be elucidated. Here, we identify RAB12 as a robust LRRK2 substrate in the mouse brain through phosphoproteomics profiling and solve the structure of RAB12-LRRK2 protein complex through Cryo-EM analysis.

RAB12-LRRK2 Complex Suppresses Primary Ciliogenesis and Regulates Centrosome Homeostasis in Astrocytes.

Leucine-rich repeat kinase 2 (LRRK2) phosphorylates a subset of RAB GTPases, and the phosphorylation levels are elevated by Parkinson's disease (PD)-linked mutations of LRRK2. However, the precise function of the specific RAB GTPase targeted by LRRK2 signaling in the brain remains to be elucidated. Here, we identify RAB12 as a robust LRRK2 substrate in the mouse brains through phosphoproteomics profiling and solve the structure of RAB12-LRRK2 protein complex through Cryo-EM analysis.

Ultrasensitive detection of aggregated α-synuclein using quiescent seed amplification assay for the diagnosis of Parkinson's disease.

Background: Seed amplification assays (SAA) enable the amplification of pathological misfolded proteins, including α-synuclein (αSyn), in both tissue homogenates and body fluids of Parkinson's disease (PD) patients. SAA involves repeated cycles of shaking or sonication coupled with incubation periods. However, this amplification scheme has limitations in tracking protein propagation due to repeated fragmentation.

Short-chain fatty acids suppresses astrocyte activation by amplifying Trp-AhR-AQP4 signaling in experimental autoimmune encephalomyelitis mice.

The function of astrocytes in response to gut microbiota-derived signals has an important role in the pathophysiological processes of central nervous system (CNS) diseases. However, the specific effects of microbiota-derived metabolites on astrocyte activation have not been elucidated yet. Experimental autoimmune encephalomyelitis (EAE) was induced in female C57BL/6 mice as a classical MS model.

A skin-specific α-Synuclein seeding amplification assay for diagnosing Parkinson's disease.

The seeding amplification assay (SAA) has recently emerged as a valuable tool for detecting α-synuclein (αSyn) aggregates in various clinically accessible biospecimens. Despite its efficiency and specificity, optimal tissue-specific conditions for distinguishing Parkinson's disease (PD) from non-PD outside the brain remain underexplored. This study systematically evaluated 150 reaction conditions to identify the one with the highest discriminatory potential between PD and non-synucleinopathy controls using skin samples, resulting in a modified SAA.

Inhibition of calcium-stimulated adenylyl cyclase subtype 1 (AC1) for the treatment of pain and anxiety symptoms in Parkinson's disease mice model.

Pain and anxiety are two common and undertreated non-motor symptoms in Parkinson's disease (PD), which affect the life quality of PD patients, and the underlying mechanisms remain unclear. As an important subtype of adenylyl cyclases (ACs), adenylyl cyclase subtype 1 (AC1) is critical for the induction of cortical long-term potentiation (LTP) and injury induced synaptic potentiation in the cortical areas including anterior cingulate cortex (ACC) and insular cortex (IC). Genetic deletion of AC1 or pharmacological inhibition of AC1 improved chronic pain and anxiety in different animal models.

Usp14 deficiency removes α-synuclein by regulating S100A8/A9 in Parkinson's disease.

Ubiquitin-proteasome system dysfunction triggers α-synuclein aggregation, a hallmark of neurodegenerative diseases, such as Parkinson's disease (PD). However, the crosstalk between deubiquitinating enzyme (DUBs) and α-synuclein pathology remains unclear. In this study, we observed a decrease in the level of ubiquitin-specific protease 14 (USP14), a DUB, in the cerebrospinal fluid (CSF) of PD patients, particularly females.

Splicing mutations of GALC in adult patient with adult-onset Krabbe disease: case report and review of literature.

Krabbe disease (KD) is classed as the lysosomal storage disease with mutations in the galactosylceramidase () gene, and commonly showed as autosomal recessive pattern with 30-kb deletion in infantile subtype. In this case, we report a 39-years adult-onset KD (AOKD) patient with multiple sclerosis-like symptoms and neuroimaging changes. She carries the heterozygous mutations in included a missense mutation of from her mother, and a splicing mutation of from her father.

Artesunate treats obesity in male mice and non-human primates through GDF15/GFRAL signalling axis.

Obesity, a global health challenge, is a major risk factor for multiple life-threatening diseases, including diabetes, fatty liver, and cancer. There is an ongoing need to identify safe and tolerable therapeutics for obesity management. Herein, we show that treatment with artesunate, an artemisinin derivative approved by the FDA for the treatment of severe malaria, effectively reduces body weight and improves metabolic profiles in preclinical models of obesity, including male mice with overnutrition-induced obesity and male cynomolgus macaques with spontaneous obesity, without inducing nausea and malaise.

Phosphorylation of AQP4 by LRRK2 R1441G impairs glymphatic clearance of IFNγ and aggravates dopaminergic neurodegeneration.

Aquaporin-4 (AQP4) is essential for normal functioning of the brain's glymphatic system. Impaired glymphatic function is associated with neuroinflammation. Recent clinical evidence suggests the involvement of glymphatic dysfunction in LRRK2-associated Parkinson's disease (PD); however, the precise mechanism remains unclear.

Arctigenin attenuated spatial memory impairment in pR5 mice by regulating mitochondrial energy metabolism.

Objectives: Arctigenin (ATG) is a natural product with a variety of biological activity, which can improve the pathological changes of Alzheimer's disease (AD) model mice through multiple mechanisms. This study aims to further elucidate the potential mechanism by which ATG improves memory impairment in AD mice.

Methods: Here, we used pR5 mice as an experimental model, and ATG was administered continuously for 90 days.

The Role of T Cells in Alzheimer's Disease Pathogenesis.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder associated with memory decline and cognitive impairment, which is related to hallmark protein aggregates, amyloid-β (Аβ) plaques and neurofibrillary tangles; the latter are accumulated with hyperphosphorylated Tau protein. Immune cells play an important role in AD pathogenesis. Although the role of T cells in AD remains controversial, studies have shown that T cell deficiency is associated with increased AD pathology.

Identifying , and as Baicalein's Potential Hub Targets in Parkinson's Disease-related α-synuclein-mediated Pathways by Integrated Bioinformatics Strategies.

Background: The overexpression, accumulation, and cell-to-cell transmission of α-synuclein leads to the deterioration of Parkinson's disease (PD). Previous studies suggest that Baicalein (BAI) can bind to α-synuclein and inhibit α-synuclein aggregation and secretion. However, it is still unclear whether BAI can intervene with the pathogenic molecules in α-synuclein-mediated PD pathways beyond directly targeting α-synuclein per se.

Sublobar resection reduces the risk of postoperative cognitive dysfunction compared with lobectomy.

Objectives: Sublobar resection, including wedge resection and segmentectomy, is non-inferior to lobectomy in early-stage non-small cell lung cancer treatment. We aimed to compare the risk of postoperative cognitive dysfunction (POCD) between sublobar resection and lobectomy.

Methods: We conducted a prospective cohort study.

Lipid Metabolism Disorder in Cerebrospinal Fluid Related to Parkinson's Disease.

Background: Abnormal accumulation of lipids is found in dopamine neurons and resident microglia in the substantia nigra of patients with Parkinson's disease (PD). The accumulation of lipids is an important risk factor for PD. Previous studies have mainly focussed on lipid metabolism in peripheral blood, but little attention has been given to cerebrospinal fluid (CSF).

Correlation of SV2C rs1423099 single nucleotide polymorphism with sporadic Parkinson's disease in Han population in Southern China.

Background: The synaptic vesicle glycoprotein 2 (SV2) has been implicated in synaptic function throughout the brain. Accumulating evidence investigated that SV2C contributed to dopamine release and the disrupted expression of SV2C was considered to be a unique feature of PD that may facilitate dopaminergic neuron dysfunction.

Objective: This study aimed to examine the relationship between the SV2C rs1423099 single nucleotide polymorphism and sporadic Parkinson's disease (PD) in the Chinese Han population.

CHCHD2 Thr61Ile mutation impairs F1F0-ATPase assembly in and models of Parkinson's disease.

Mitochondrial dysfunction is a significant pathological alteration that occurs in Parkinson's disease (PD), and the Thr61Ile (T61I) mutation in coiled-coil helix coiled-coil helix domain containing 2 (CHCHD2), a crucial mitochondrial protein, has been reported to cause Parkinson's disease. F1F0-ATPase participates in the synthesis of cellular adenosine triphosphate (ATP) and plays a central role in mitochondrial energy metabolism. However, the specific roles of wild-type (WT) CHCHD2 and T61I-mutant CHCHD2 in regulating F1F0-ATPase activity in Parkinson's disease, as well as whether CHCHD2 or CHCHD2 T61I affects mitochondrial function through regulating F1F0-ATPase activity, remain unclear.

Low and high doses of oral maslinic acid protect against Parkinson's disease via distinct gut microbiota-related mechanisms.

The use of oral agents that can modify the gut microbiota (GM) could be a novel preventative or therapeutic option for Parkinson's disease (PD). Maslinic acid (MA), a pentacyclic triterpene acid with GM-dependent biological activities when it is taken orally, has not yet been reported to be effective against PD. The present study found both low and high dose MA treatment significantly prevented dopaminergic neuronal loss in a classical chronic PD mouse model by ameliorating motor functions and improving tyrosine hydroxylase expressions in the substantia nigra pars compacta (SNpc) and increasing dopamine and its metabolite homovanillic acid levels in the striatum.