Expression of G2019S LRRK2 in Rat Primary Astrocytes Mediates Neurotoxicity and Alters the Dopamine Synthesis Pathway in N27 Cells via Astrocytic Proinflammatory Cytokines and Neurotrophic Factors.

Astrocytes in the brain contribute to various essential functions, including maintenance of the neuronal framework, survival, communication, metabolic processes, and neurotransmitter levels. Leucine-rich repeat kinase 2 (LRRK2) is associated with the pathogenesis of Parkinson's disease (PD). LRRK2 is expressed in neurons, microglia, and astrocytes and plays diverse roles in these cell types.

Nuclear α-Synuclein-Derived Cytotoxic Effect via Altered Ribosomal RNA Processing in Primary Mouse Embryonic Fibroblasts.

α-Synuclein (αSyn) is an important player in Parkinson's disease (PD) pathogenesis. The aggregation of αSyn is mainly formed in the cytoplasm, whereas some αSyn accumulation has also been found in the nuclei of neurons. To assess the effect of nuclear αSyn, we generated αSyn conjugated with a nuclear export signal (NES) or a nuclear localization signal (NLS), and compared them with wild-type αSyn in primary mouse embryonic fibroblasts (MEF) using DNA transfection.

A Study on the Skin Irritation Toxicity Test of Processed Sulfur in New Zealand White Rabbit.

Objectives: This study was performed to evaluate the skin irritation toxicity of processed sulfur.

Methods: All experiments were conducted at Medvill (Korea), an institution authorized to perform non-clinical studies, under the Good Laboratory Practice (GLP) regulations. In order to investigate skin irritation toxicity of processed sulfur, we divided the back of six rabbits into two control sites and two test sites.

LRRK2 Inhibition Mitigates the Neuroinflammation Caused by TLR2-Specific α-Synuclein and Alleviates Neuroinflammation-Derived Dopaminergic Neuronal Loss.

Evidence suggests that crosstalk occurs between microglial leucine-rich repeat kinase 2 (LRRK2)-a regulator of neuroinflammation-and neuron-released α-synuclein (αSyn)-a promoter of microglial activation and neuroinflammatory responses-in neuroinflammation-mediated Parkinson's disease (PD) progression. Therefore, we examined whether LRRK2 inhibition reduces the responses of microglia to neuroinflammation caused by neuron-released αSyn. We examined the neuroinflammatory responses provoked by Toll-like receptor 2 (TLR2)-positive αSyn of neuronal cells using an LRRK2 inhibitor in the mouse glioma cells, rat primary microglia, and human microglia cell line; and the effects of LRRK2 inhibitor in the co-culture of ectopic αSyn-expressing human neuroblastoma cells and human microglia cells and in mouse models by injecting αSyn.

Systematic Review of Diagnostic Tools and Interventions for Sarcopenia.

Diagnosis of rare incurable diseases is important. Specific evaluation methods and standards for sarcopenia differ according to each sarcopenia-related medical association. This study aimed to identify the tools that are currently used to diagnose sarcopenia and to systematically review various interventions for sarcopenia.

Psychosocial Factors Related to Stroke Patients' Rehabilitation Motivation: A Scoping Review and Meta-Analysis Focused on South Korea.

The incidence of strokes in individuals in their 30-40 s-who have responsibilities towards their families-has increased. Additionally, many stroke patients suffer from post-stroke disabilities and require rehabilitation. However, especially in younger stroke patients, factors such as financial burden and the inability to be productive lead to depression and thereby, the lack of rehabilitation motivation-which affects their therapeutic outcomes.

LRRK2 Kinase Inhibitor Rejuvenates Oxidative Stress-Induced Cellular Senescence in Neuronal Cells.

Background: Leucine-rich repeat kinase 2 (LRRK2) plays a critical role in the pathogenesis of Parkinson's disease (PD). Aging is the most critical risk factor for the progression of PD. The correlation between aging and cellular senescence has been established.

Ciliogenesis is Not Directly Regulated by LRRK2 Kinase Activity in Neurons.

Mutations in the Leucine-rich repeat kinase 2 () gene are the most prevalent cause of familial Parkinson's disease (PD). The increase in LRRK2 kinase activity observed in the pathogenic G2019S mutation is important for PD development. Several studies have reported that increased LRRK2 kinase activity and treatment with LRRK2 kinase inhibitors decreased and increased ciliogenesis, respectively, in mouse embryonic fibroblasts (MEFs) and retinal pigment epithelium (RPE) cells.

Expression of transduced nucleolin promotes the clearance of accumulated α-synuclein in rodent cells and animal model.

Alpha-synuclein (αSyn) is a major component of Lewy bodies, which are a known pathogenic marker of Parkinson's disease (PD). The dysfunction of protein degradation machinery causes αSyn accumulation. The reinforcement of αSyn degradation is a potential therapeutic target for PD because accumulated αSyn is responsible for the pathogenesis of PD.

Analysis of α-synuclein levels related to LRRK2 kinase activity: from substantia nigra to urine of patients with Parkinson's disease.

Research on Parkinson's disease (PD) has been focused on the development of PD diagnostic tools as much as the development of PD therapeutics. Several genetic culprits of PD, including DJ-1, Leucine-rich repeat kinase 2 (LRRK2), and α-synuclein (α-syn), have been investigated as markers of PD in human biofluids. Unfortunately, the approaches to develop PD diagnostic tools are impractical, and there is a considerable demand for an appropriate marker of PD.

A systematic literature review and meta-analysis of the clinical effects of aroma inhalation therapy on sleep problems.

Background: This systematic review investigated the clinical effects of inhalation aromatherapy for the treatment of sleep problems such as insomnia.

Methods: Studies on sleep problems and inhalation aromatherapy, published in Korean and international journals, were included in the meta-analysis. Five domestic and international databases, respectively each, were used for the literature search.

Urinary Biomarkers for Neurodegenerative Diseases.

Global incidence of neurodegenerative diseases (NDDs) such as Alzheimer's disease (AD) and Parkinson's disease (PD) is rapidly increasing, but the diagnosis of these diseases at their early stage is challenging. Therefore, the availability of reproducible and reliable biomarkers to diagnose such diseases is more critical than ever. In addition, biomarkers could be used not only to diagnose diseases but also to monitor the development of disease therapeutics.

Detection and Assessment of α-Synuclein Oligomers in the Urine of Parkinson's Disease Patients.

Background: α-Synuclein (α-syn) is a major component of Lewy bodies, a pathologic marker of Parkinson's disease (PD) in post-mortem studies. The use of α-syn as a practical PD biomarker has been investigated by numerous researchers. However, reports of differences in α-syn levels in biofluids, such as cerebrospinal fluid, plasma, and saliva, between PD patients and controls are inconsistent.

Korean Traditional Medicine in Treating Patients with Mild Cognitive Impairment: A Multicenter Prospective Observational Case Series.

In Korea, patients with mild cognitive impairment can choose to receive treatment of Korean medicine, and Korean medicine hospitals provide specialized medical care for the prevention and management of cognitive disorders. The aim of the study is to explore the role of Korean medicine therapy for patients with mild cognitive impairment in a real clinical setting. Fifteen patients with amnestic mild cognitive impairment were enrolled in this prospective observational study in three Korean medicine hospitals.

Safety and efficacy of Jujadokseo-hwan for memory deficit (amnesia) in mild neurocognitive disorder: A protocol for randomized, double-blind, placebo-controlled, parallel-group, multicenter clinical trial.

Background: Mild neurocognitive disorder (mNCD) is one of the degenerative diseases that results in memory deficit, and can progress to dementia. The effectiveness of drug therapy for mNCD is still debatable, but treatment of this disease has important implications for postponing or preventing dementia. Jujadokseo-hwan (JDH) is a traditional herbal medicine formulation that exhibits improvement in cognitive abilities and neuroprotective effects.

26-Week Repeated Dose Oral Toxicity Study of KCHO-1 in Sprague-Dawley Rats.

Objectives: KCHO-1(Mecasin), also called Gamijakyakgamchobuja-tang originally, is a combination of some traditional herbal medicines in East Asia. This medicine has been used mainly for alleviating neuropathic pains for centuries in Korean traditional medicine. KCHO-1 was developed to treat pain, joint contracture and muscular weakness in patients with amyotrophic lateral sclerosis.

Validation of the Core Seven-Emotions Inventory - short form.

Background: This study aimed to evaluate the reliability and validity of short form of the Core Seven Emotions Inventory (CSEI-s) scale.

Methods: The participants were third-grade Korean Medicine University students As with the original CSEI, the scales in the short form (CSEI-s) were composed of seven factors and consisted of 28 items in total. The internal consistency coefficient was calculated, and a confirmatory factor analysis was conducted to verify the reliability of the short form scale.

Rab GTPases as Physiological Substrates of LRRK2 Kinase.

LRRK2 (Leucine-Rich Repeat Kinase 2) is a gene whose specific mutations cause Parkinson's disease (PD), the most common neurodegenerative movement disorder. LRRK2 harbors GTPase and kinase activities, two enzyme activities that play critical roles in the regulation of cellular signal transduction. Among the several LRRK2 pathogenic mutations, the most prevalent G2019S mutation increases its kinase activity when compared with the wild-type (WT), suggesting that LRRK2 kinase substrates are potential culprits of PD pathogenesis.

G2019s LRRK2 promotes mitochondrial fission and increases TNFα-mediated neuroinflammation responses.

Leucine rich-repeat kinase 2 (LRRK2) is involved in the pathogenesis of Parkinson's disease (PD). LRRK2 has kinase and GTPase activities, and mediates several cell functions, including vesicle trafficking, apoptosis, autophagy, mitochondrial dynamics, and neuroinflammation. G2019S (GS) is the most prevalent mutation of LRRK2.

Upregulation of the p53-p21 pathway by G2019S LRRK2 contributes to the cellular senescence and accumulation of α-synuclein.

Parkinson's disease (PD) is characterized by the degeneration of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies (LB) in neurons. α-Synuclein (αSyn) is a major component of LB and promote the PD pathogenesis via its accumulation by the impaired proteasomal or autophagic clearance. Numerous studies have revealed that the reduction of proteasome activity and autophagy is accelerated by cellular senescence.

Clinical effects of mindfulness meditation and cognitive behavioral therapy standardized for insomnia: A protocol for a systematic review and meta-analysis.

Introduction: This systematic review protocol describes the methods that will be used to evaluate the efficacy and safety of mindfulness meditation and cognitive behavioral therapy programs as a psychological intervention for insomnia disorders.

Methods And Analysis: We will search the following 11 electronic databases without language or publication status restrictions: MEDLINE, the Cochrane Central Register of Controlled Trials, EMBASE, Allied and Complementary Medicine Database, Cumulative Index to Nursing and Allied Health Literature, and PsycARTICLES. Furthermore, we will also search 5 Korean-language databases (Oriental Medicine Advanced Searching Integrated System, Korean studies Information Service System, Research Information Service System, Korean Medical Database, and Korea Citation Index).

Increase in anti-apoptotic molecules, nucleolin, and heat shock protein 70, against upregulated LRRK2 kinase activity.

Leucine-rich repeat kinase 2 (LRRK2) is involved in Parkinson's disease (PD) pathology. A previous study showed that rotenone treatment induced apoptosis, mitochondrial damage, and nucleolar disruption via up-regulated LRRK2 kinase activity, and these effects were rescued by an LRRK2 kinase inhibitor. Heat-shock protein 70 (Hsp70) is an anti-oxidative stress chaperone, and overexpression of Hsp70 enhanced tolerance to rotenone.

Characterization of Parkinson's disease-related pathogenic TMEM230 mutants.

Parkinson's disease (PD) is the second most common neurodegenerative disease. Although most PD cases are sporadic, 5-10% of them are hereditary and several pathogenic mutations in related genes have been identified. Mutations in were recently identified as a cause of autosomal dominant PD.