Erratum: Correction of Text in the Article "Effects of Hormone Replacement Therapy on Bone Mineral Density in Korean Adults With Turner Syndrome".

This corrects the article on p. e9 in vol. 39, PMID: 38193328.

Effects of Hormone Replacement Therapy on Bone Mineral Density in Korean Adults With Turner Syndrome.

BACKGROUND: Turner syndrome (TS) is a common chromosomal abnormality, which is caused by loss of all or part of one X chromosome. Hormone replacement therapy in TS is important in terms of puberty, growth and prevention of osteoporosis however, such a study has never been conducted in Korea. Therefore, the purpose of our study was to determine relationship between the starting age, duration of estrogen replacement therapy (ERT) in TS and develop a hormone replacement protocol suitable for the situation in Korea. METHODS: This is retrospective study analyzed the medical records in TS patients treated at the Severance hospital, Yonsei University College of Medicine, Seoul, Korea from 1997 to 2019. Total of 188 subjects who had received a bone density test at least once were included in the study. Korean National Health and Nutrition Examination Survey (KNHANES) was used for achieving bone mineral density (BMD) of normal control group. Student's t-test, Mann-Whitney U test, ANOVA and correlation analysis were performed using SPSS 18.0. RESULTS: Each BMD measurement was significantly lower in women with TS than in healthy Korean women. Early start and longer duration of ERT is associated with higher lumbar spine BMD but not femur neck BMD. Femur neck BMD, but not lumbar spine BMD was significantly higher in women with mosaicism than 45XO group. CONCLUSION: Early onset and appropriate duration of hormone replacement therapy is important for increasing bone mineral density in patients with Turner syndrome. Also, ERT affects differently to TS patients according to mosaicism.

NK cells clear α-synuclein and the depletion of NK cells exacerbates synuclein pathology in a mouse model of α-synucleinopathy.

The pathological hallmark of synucleinopathies, including Lewy body dementia and Parkinson's disease (PD), is the presence of Lewy bodies, which are primarily composed of intracellular inclusions of misfolded α-synuclein (α-syn) among other proteins. α-Syn is found in extracellular biological fluids in PD patients and has been implicated in modulating immune responses in the central nervous system (CNS) and the periphery. Natural killer (NK) cells are innate effector lymphocytes that are present in the CNS in homeostatic and pathological conditions. NK cell numbers are increased in the blood of PD patients and their activity is associated with disease severity; however, the role of NK cells in the context of α-synucleinopathies has never been explored. Here, we show that human NK cells can efficiently internalize and degrade α-syn aggregates via the endosomal/lysosomal pathway. We demonstrate that α-syn aggregates attenuate NK cell cytotoxicity in a dose-dependent manner and decrease the release of the proinflammatory cytokine, IFN-γ. To address the role of NK cells in PD pathogenesis, NK cell function was investigated in a preformed fibril α-syn-induced mouse PD model. Our studies demonstrate that in vivo depletion of NK cells in a preclinical mouse PD model resulted in exacerbated motor deficits and increased phosphorylated α-syn deposits. Collectively, our data provide a role of NK cells in modulating synuclein pathology and motor symptoms in a preclinical mouse model of PD, which could be developed into a therapeutic for PD and other synucleinopathies.

Sex- and age-dependent alterations of splenic immune cell profile and NK cell phenotypes and function in C57BL/6J mice.

BACKGROUND: Physiological homeostasis decline, immunosenescence, and increased risk for multiple diseases, including neurodegeneration, are all hallmarks of ageing. Importantly, it is known that the ageing process is sex-biased. For example, there are sex differences in predisposition for multiple age-related diseases, including neurodegenerative and autoimmune diseases. However, sex differences in age-associated immune phenotypes are not clearly understood. RESULTS: Here, we examined the effects of age on immune cell phenotypes in both sexes of C57BL/6J mice with a particular focus on NK cells. We found female-specific spleen weight increases with age and concordant reduction in the number of splenocytes per gram of spleen weight compared to young females. To evaluate sex- and age-associated changes in splenic immune cell composition, we performed flow cytometry analysis. In male mice, we observed an age-associated reduction in the frequencies of monocytes and NK cells; female mice displayed a reduction in B cells, NK cells, and CD8 + T cells and increased frequency of monocytes and neutrophils with age. We then performed a whole blood stimulation assay and multiplex analyses of plasma cytokines and observed age- and sex-specific differences in immune cell reactivity and basal circulating cytokine concentrations. As we have previously illustrated a potential role of NK cells in Parkinson's disease, an age-related neurodegenerative disease, we further analyzed age-associated changes in NK cell phenotypes and function. There were distinct differences between the sexes in age-associated changes in the expression of NK cell receptors, IFN-γ production, and impairment of α-synuclein endocytosis. CONCLUSIONS: This study demonstrates sex- and age-specific alterations in splenic lymphocyte composition, circulating cytokine/chemokine profiles, and NK cell phenotype and effector functions. Our data provide evidence that age-related physiological perturbations differ between the sexes which may help elucidate sex differences in age-related diseases, including neurodegenerative diseases, particularly Parkinson's disease, where immune dysfunction is implicated in their etiology.

Application of Testing-Tracing-Treatment Strategy in Response to the COVID-19 Outbreak in Seoul, Korea.

BACKGROUND: Following the coronavirus disease 2019 (COVID-19) outbreak in Wuhan, China, a total of 637 patients had been diagnosed with the disease in Seoul as of May 2, 2020. Our study aimed to describe the impact of the 3T strategies (preemptive testing, prompt tracing and proper treatment) on the epidemiological characteristics of COVID-19 in Seoul. METHODS: The descriptive and explanatory analysis was carried out on critical indicators such as epidemiological characteristics and key duration of patient status change from January 24 to May 2 in Seoul before and after preemptive testing for patients under investigation associated with COVID-19 clusters. RESULTS: Preemptive testing increased the positive test rate (3.9% to 4.2%), an asymptomatic case at diagnosis (16.9% to 30.6%), and reduced the time from symptom onset to quarantine (4.0 to 3.0 days). Prompt tracing decreased unknown sources of infection (6.9% to 2.8%), the mean number of contacts (32.2 to 23.6), and the time-varying reproduction number R(t) (1.3 to 0.6). With proper treatment, only 2 cases of mortality occurred, resulting in a fatality rate of just 0.3%. CONCLUSION: In the first wave of the COVID-19 pandemic lasting 100 days, the effect of the 3T strategies flattened the curve and decreased the time during which infected individuals were contagious, thereby lowering the R(t) below 1 in Seoul.

Intrastriatal injection of preformed alpha-synuclein fibrils alters central and peripheral immune cell profiles in non-transgenic mice.

Parkinson's disease (PD) is characterized by the accumulation of alpha-synuclein (α-syn) inclusions, the major component of Lewy bodies. Extracellular α-syn aggregates act as a damage-associated molecular pattern (DAMP) and the presence of autoantibodies against α-syn species in the cerebrospinal fluid and the serum of PD patients implicate the involvement of innate and adaptive immune responses. In non-transgenic (Tg) mice, intrastriatal injection of preformed fibril (PFF) α-syn results in widespread pathologic α-syn inclusions in the CNS. While the PFF model has been broadly utilized to study the mechanistic relationship between α-syn transmission and other neuropathological phenotypes, the immune phenotypes in this model are not clearly demonstrated. This study aimed to characterize the immune phenotypes during pathologic α-syn propagation by utilizing PFF α-syn-injected non-tg mice. Here, we showed that pathologic α-syn inclusions are prevalent in various brain regions and the gut at 5 months post injection (p.i.), preceding the degeneration of dopaminergic neurons in substantia nigra (SN). We discovered a distinct inflammatory response involving both activation of microglia and astrocytes and infiltration of B, CD4+ T, CD8+ T, and natural killer cells in the brain at 5 months p.i. Moreover, PFF α-syn-injected mice display significant alterations in the frequency and number of leukocyte subsets in the spleen and lymph nodes with minimum alterations in the blood. Our data provide primary evidence that intracerebral-initiated synucleinopathies in non-tg mice alter immune cell profiles both in the CNS and peripheral lymphoid organs. Furthermore, our data provides support for utilizing this mouse model to assess the mechanistic connection between immune responses and synuclein pathology.

Neighborhood decline and mixed land uses: mitigating housing abandonment in shrinking cities.

Neighborhood decline is a critical issue in shrinking cities. Components of sustainable urbanism such as mixed land uses have risen as possible urban planning-based approaches to help mitigate urban and neighborhood decline. This research identifies examines if mixed land uses can help mitigate urban decline by using the tax delinquent status of single family houses as a proxy for decline in Dayton, Ohio, USA. Logistic regression models are utilized to estimate the probability of tax delinquency. The results suggest that the proximity to mixed land uses is associated with increasing or decreasing the probability of tax delinquent for single family lots. The number of commercial and industrial lots in a neighborhood also has effects on the probability of a lot becoming tax delinquent, but the specific types of commercial and industrial lots dictate the direction of effects. The existence of commercial apartment lots, retail lots, and industrial food and drink plant lots were shown to help decrease the probability of tax delinquent lots. Also, decreasing the amount of property tax applied to parcels can help to limit distress in neighborhoods. This research contributes to the ongoing efforts to stymie the amount of residential abandonment in depopulating and declining cities.

National NO2 exposure models for measuring its impact on vulnerable people in the US metropolitan areas.

Epidemiological research requires accurate prediction of the concentrations of air pollutants. In this study, satellite-based estimates (OMI NO2), distance-weighted models (DWMs), and universal kriging (UK) are applied to land use regression (LUR) to predict annually and monthly averaged NO2 concentrations in the continental United States. In addition, to assess environmental risk, the relationship between NO2 concentrations and people potentially exposed to NO2 within urban areas is explored in 377 metropolitan statistical areas (MSAs). The results of this study show that the application of a combination of OMI NO2, UK, and DWMs to LUR yielded the highest cross-validated (CV) R2 values and the lowest root mean square error of prediction (RMSEP): 82.9% and 0.392 on a square root scale of ppb in the annual model and 70.4-83.5% and 0.408-0.518 on square root scale of ppb in the monthly models, respectively. Moreover, the model presented a spatially unbiased distribution of CV error terms. Models based on LUR provided more accurate NO2 predictions with lower RMSEP in urban areas than in rural areas. In addition, this study finds that the people living in the urban areas of MSAs, with larger populations and a higher percentage of children under 18 years of age, are likely to be exposed to higher NO2 concentrations. By contrast, people living in the urban areas of MSAs with a higher percentage of the elderly over 65 years of age are likely to be exposed to lower NO2 concentrations.

RGS10 deficiency ameliorates the severity of disease in experimental autoimmune encephalomyelitis.

BACKGROUND: Regulator of G-protein signaling (RGS) family proteins, which are GTPase accelerating proteins (GAPs) that negatively regulate G-protein-coupled receptors (GPCRs), are known to be important modulators of immune cell activation and function. Various single-nucleotide polymorphisms in RGS proteins highly correlate with increased risk for multiple sclerosis (MS), an autoimmune, neurodegenerative disorder. An in-depth search of the gene expression omnibus profile database revealed higher levels of RGS10 and RGS1 transcripts in peripheral blood mononuclear cells (PBMCs) in MS patients, suggesting potential functional roles for RGS proteins in MS etiology and/or progression. METHODS: To define potential roles for RGS10 in regulating autoimmune responses, we evaluated RGS10-null and wild-type (WT) mice for susceptibility to experimental autoimmune encephalomyelitis (EAE), a widely studied model of MS. Leukocyte distribution and functional responses were assessed using biochemical, immunohistological, and flow cytometry approaches. RESULTS: RGS10-null mice displayed significantly milder clinical symptoms of EAE with reduced disease incidence and severity, as well as delayed onset. We observed fewer CD3+ T lymphocytes and CD11b+ myeloid cells in the central nervous system (CNS) tissues of RGS10-null mice with myelin oligodendrocyte protein (MOG)35-55-induced EAE. Lymph node cells and splenocytes of immunized RGS10-null mice demonstrated decreased proliferative and cytokine responses in response to in vitro MOG memory recall challenge. In adoptive recipients, transferred myelin-reactive RGS10-null Th1 cells (but not Th17 cells) induced EAE that was less severe than their WT counterparts. CONCLUSIONS: These data demonstrate a critical role for RGS10 in mediating autoimmune disease through regulation of T lymphocyte function. This is the first study ever conducted to elucidate the function of RGS10 in effector lymphocytes in the context of EAE. The identification of RGS10 as an important regulator of inflammation might open possibilities for the development of more specific therapies for MS.

Recombinant tissue plasminogen activator promotes, and progesterone attenuates, microglia/macrophage M1 polarization and recruitment of microglia after MCAO stroke in rats.

BACKGROUND: Tissue plasminogen activator (tPA) is one of the few approved treatments for stroke, but its effects on the phenotype of microglia/macrophages are poorly understood. One of its side effects is an increase in the inflammatory response leading to neuronal cell damage and death in the ischemic cascade after stroke. Injury-induced activated microglia/macrophages can have dual functions as pro-inflammatory (M1) and anti-inflammatory (M2) factors in brain injury and repair. Recent studies show that progesterone (PROG) is a potent anti-inflammatory agent which affects microglia/macrophage expression after brain injury. PURPOSE: We examined the interaction of tPA-induced expression of microglia/macrophage phenotypes and PROG's anti-inflammatory effects. RESULTS: tPA treatment increased the recruitment of microglia/macrophages, the polarity of M1 reactions, the expression of MIP-1α in neurons and capillaries, and the expression of MMP-3 compared to vehicle, and PROG modulated these effects. CONCLUSIONS: PROG treatment attenuates tPA-induced inflammatory alterations in brain capillaries and microglia/macrophages both in vivo and in vitro and thus may be a useful adjunct therapy when tPA is given for stroke.

Effect of midazolam on cardiopulmonary function during colonoscopy with conscious sedation.

BACKGROUND AND AIM: Conscious sedation of patients with midazolam reduces anxiety and pain and improves colonoscopy success rates. However, it may lead to adverse effects such as hypoxia and hypotension. The present study investigated the effects of midazolam on cardiopulmonary function during colonoscopy with conscious sedation. METHODS: Between January 2011 and September 2011, 126 consecutive patients undergoing colonoscopy were enrolled and divided into two groups: (i) sedation with midazolam (midazolam group, n=65); and (ii) no sedation (control group, n=61). Systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), and peripheral oxygen saturation (SpO(2) ), were recorded before, during and after the endoscopic procedure. RESULTS: In the midazolam group, SBP and DBP decreased more during colonoscopy than in the control group. However, the frequency of a significant change in SBP was similar in both groups. During colonoscopy, HR and SpO(2) decreased significantly in the midazolam group compared to those in the control group. SpO(2) levels returned to normal after the procedure. CONCLUSIONS: Midazolam induced decreases in SBP, DBP, HR and SpO(2) during colonoscopy. Clinically significant changes in SBP, HR, and SpO(2) , however, were similar in the midazolam and control groups. These results suggest that midazolam has a tolerable effect on cardiopulmonary function and may be safely used during colonoscopy.

RGS10 mitigates high glucose-induced microglial inflammation via the reactive oxidative stress pathway and enhances synuclein clearance in microglia.

Microglia play a critical role in maintaining brain homeostasis but become dysregulated in neurodegenerative diseases. Regulator of G-protein Signaling 10 (RGS10), one of the most abundant homeostasis proteins in microglia, decreases with aging and functions as a negative regulator of microglia activation. RGS10-deficient mice exhibit impaired glucose tolerance, and high-fat diet induces insulin resistance in these mice. In this study, we investigated whether RGS10 modulates microglia activation in response to hyperglycemic conditions, complementing our previous findings of its role in inflammatory stimuli. In RGS10 knockdown (KD) BV2 cells, TNF production increased significantly in response to high glucose, particularly under proinflammatory conditions. Additionally, glucose uptake and GLUT1 mRNA levels were significantly elevated in RGS10 KD BV2 cells. These cells produced higher ROS and displayed reduced sensitivity to the antioxidant N-Acetyl Cysteine (NAC) when exposed to high glucose. Notably, both BV2 cells and primary microglia that lack RGS10 exhibited impaired uptake of alpha-synuclein aggregates. These findings suggest that RGS10 acts as a negative regulator of microglia activation not only in response to inflammation but also under hyperglycemic conditions.

Distinctive CD56dim NK subset profiles and increased NKG2D expression in blood NK cells of Parkinson's disease patients.

Mounting data suggest an important role for the immune system in Parkinson's disease (PD). Previous evidence of increased natural killer (NK) cell populations in PD suggests a potential role of NK cells in the pathogenesis of the disease. Previous studies have analyzed NK cell populations using aggregation by variable expression of CD56 and CD16. It remains unknown what differences may exist between NK cell subpopulations when stratified using more nuanced classification. Here, we profile NK cell subpopulations and elucidate the expressions of activating, NKG2D, inhibitory, NKG2A, and homing, CX3CR1, receptors on NK cell subpopulations in PD and healthy controls (HC). We analyzed cryopreserved PMBC samples using a 10-color flow cytometry panel to evaluate NK cell subpopulations in 31 individuals with sporadic PD and 27 HC participants. Here we identified significant differences in the CD56dim NK subset that changes with disease severity in PD. Furthermore, the expressions of NKG2D in all three NK cell subsets were significantly elevated in PD patients compared to HC. Notably, NKG2A expression in the CD56bright NK subset increased in PD patients with longer disease duration but there were no changes in CX3CR1. In summary, our data suggests that changes in NK cells may be influenced by the clinical severity and duration of PD.

Simulating the Spatial Impacts of a Coastal Barrier in Galveston Island, Texas: A Three-Dimensional Urban Modeling Approach.

Due to its vulnerability to hurricanes, Galveston Island, TX, USA, is exploring the implementation of a coastal surge barrier (also referred to as the "Ike Dike") for protection from severe flood events. This research evaluates the predicted effects that the coastal spine will have across four different storm scenarios, including a Hurricane Ike scenario and 10-year, 100-year, and 500-year storm events with and without a 2.4ft. sea level rise (SLR). To achieve this, we develop a 1:1 ratio, 3-dimensional urban model and ran real-time flood projections using ADCIRC model data with and without the coastal barrier in place. Findings show that inundated area and property damages due to flooding will both significantly decrease if the coastal spine is implemented, with a 36% decrease in the inundated area and $4 billion less in property damage across all storm scenarios, on average. When including SLR, the amount of protection of the Ike Dike diminishes due to flooding from the bay side of the island. While the Ike Dike does appear to offer substantial protection from flooding in the short term, integrating the coastal barrier with other non-structural mechanisms would facilitate more long-term protection when considering SLR.

The Concise Guide to PHARMACOLOGY 2023/24: Introduction and Other Protein Targets.

The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of approximately 1800 drug targets, and about 6000 interactions with about 3900 ligands. There is an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes almost 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.16176. In addition to this overview, in which are identified 'Other protein targets' which fall outside of the subsequent categorisation, there are six areas of focus: G protein-coupled receptors, ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2023, and supersedes data presented in the 2021/22, 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.

Regulator of G-protein signaling-10 negatively regulates NF-κB in microglia and neuroprotects dopaminergic neurons in hemiparkinsonian rats.

Microglia are the brain-resident macrophages responsible for immune surveillance that become activated in response to injury, infection, environmental toxins, and other stimuli that threaten neuronal survival. Previous work from our group demonstrated that mice deficient in Regulator of G-protein Signaling 10 (RGS10), a microglia-enriched GTPase activating protein (GAP) for G-protein α subunits, displayed increased microglial burden in the CNS at birth and developed a parkinsonian phenotype after exposure to chronic systemic inflammation, implicating a neuroprotective role for RGS10 in the nigrostriatal pathway. While it is known that RGS10 is expressed in both microglia and certain subsets of neurons, it is not known whether RGS10 functions similarly in both cells types. In this study we sought to delineate the specific role of RGS10 in microglia and identify the molecular pathway(s) required for RGS10 to exert its actions in microglia. Here, we identify RGS10 as a negative regulator of the nuclear factor κB(NF-κB) pathway in microglia and demonstrate that the proinflammatory and cytotoxic phenotype of Rgs10-null microglia can be reversed by lentiviral-mediated restoration of RGS10 expression. In vivo gene transfer of RGS10 into the substantia nigra pars compacta (SNpc) of rats reduced microgliosis and protected against 6-OHDA neurotoxin-induced death of dopaminergic (DA) neurons. Together, our findings suggest that modulation of RGS10 activity in microglia may afford therapeutic benefit in the treatment of chronic neuroinflammatory conditions as well as neuroprotection against inflammation-related degeneration in Parkinson's disease (PD), the second most common neurodegenerative disorder affecting individuals over age 65.

Regulation of microglia effector functions by tumor necrosis factor signaling.

The exact biological role of the cytokine tumor necrosis factor (TNF) in the central nervous system (CNS) is not well understood; but overproduction of TNF by activated microglia has been implicated in neuronal death, suggesting that TNF inhibition in the CNS may be a viable neuroprotective strategy. We investigated the role of TNF signaling in regulation of microglia effector functions using molecular, cellular, and functional analyses of postnatal and adult microglia populations in the CNS. No differences were found by flow cytometric analyses in the basal activation state between TNF-null and wild-type mice. Although TNF-null microglia displayed an atypical morphology with cytoplasmic vacuoles in response to stimulation with lipopolysaccharide (LPS), the phagocytic response of TNF-null microglia to Escherichia coli particles in vitro was normal and there were no signs of enhanced caspase 3 activation or apoptosis. Functionally, conditioned media from LPS-stimulated TNF-null microglia was found to have significantly reduced levels of IL-10, IL-6, IL-1ß, IL-12, and CXCL1 relative to wild-type microglia and exerted no cytotoxic effects on neurally differentiated dopaminergic (DA) MN9D cells. In contrast, incubation of wild-type microglia with TNF inhibitors selectively depleted the levels of soluble TNF and its cytotoxicity on MN9D cells. To distinguish whether reduced cytotoxicity by LPS-activated TNF-null microglia could be attributed to deficient autocrine TNF signaling, we employed primary microglia deficient in one or both TNF receptors (TNFR1 and TNFR2) in co-culture with MN9D cells and found that neither receptor is required to elicit LPS-evoked TNF production and cytotoxicity on DA cells.

RGS10 exerts a neuroprotective role through the PKA/c-AMP response-element (CREB) pathway in dopaminergic neuron-like cells.

Regulator of G-protein signaling-10 (RGS10) is a GTPase activating protein for Gαi/q/z subunits that is highly expressed in the immune system and in a broad range of brain regions including the hippocampus, striatum, dorsal raphe, and ventral midbrain. Previously, we reported that RGS10-null mice display increased vulnerability to chronic systemic inflammation-induced degeneration of nigral dopaminergic (DA) neurons. Given that RGS10 is expressed in DA neurons, we investigated the extent to which RGS10 regulates cell survival under conditions of inflammatory stress. Because of the inherent limitations associated with use of primary DA neurons for biochemical analyses, we employed a well-characterized ventral mesencephalon DA neuroblastoma cell line (MN9D) for our studies. We found that stable over-expression of RGS10 rendered them resistant to TNF-induced cytotoxicity; whereas MN9D cells expressing mutant RGS10-S168A (which is resistant to phosphorylation by protein kinase A at a serine residue that promotes its nuclear translocation) showed similar sensitivity to TNF as the parental MN9D cells. Using biochemical and pharmacologic approaches, we identified protein kinase A and the downstream phospho-cAMP response element-binding signaling pathway (and ruled out ERK 1/2, JNK, and NFkB) as key mediators of the neuroprotective effect of RGS10 against inflammatory stress.

New Insights and Implications of Natural Killer Cells in Parkinson's Disease.

Parkinson's disease (PD) is the second most common neurodegenerative disease and is characterized by the loss of dopaminergic neurons in the substantia nigra and the abnormal aggregation and accumulation of the alpha-synuclein (α-syn) protein into Lewy bodies. It is established that there is an association between inflammation and PD; however, the time course of the inflammatory process as well as the immune cells involved are still debated. Natural killer (NK) cells are innate lymphocytes with numerous functions including targeting and killing infected or malignant cells, antimicrobial defense, and resolving inflammation. NK cell subsets differ in their effector function capacities which are modulated by activating and inhibitory receptors expressed at the cell surface. Alterations in NK cell numbers and receptor expression have been reported in PD patients. Recently, NK cell numbers and frequency were shown to be altered in the periphery and in the central nervous system in a preclinical mouse model of PD. Moreover, NK cells have recently been shown to internalize and degrade α-syn aggregates and systemic NK cell depletion exacerbated synuclein pathology in a preclinical mouse model of PD, indicating a potential protective role of NK cells. Here, we review the inflammatory process in PD with a particular focus on alterations in NK cell numbers, phenotypes, and functions.