keyword
https://read.qxmd.com/read/38378800/%C3%AE-synuclein-oligomers-potentiate-neuroinflammatory-nf-%C3%AE%C2%BAb-activity-and-induce-ca-v-3-2-calcium-signaling-in-astrocytes
#61
JOURNAL ARTICLE
Emmanouela Leandrou, Ioanna Chalatsa, Dimitrios Anagnostou, Christina Machalia, Maria Semitekolou, Vicky Filippa, Manousos Makridakis, Antonia Vlahou, Ema Anastasiadou, Kostas Vekrellis, Evangelia Emmanouilidou
BACKGROUND: It is now realized that Parkinson's disease (PD) pathology extends beyond the substantia nigra, affecting both central and peripheral nervous systems, and exhibits a variety of non-motor symptoms often preceding motor features. Neuroinflammation induced by activated microglia and astrocytes is thought to underlie these manifestations. α-Synuclein aggregation has been linked with sustained neuroinflammation in PD, aggravating neuronal degeneration; however, there is still a lack of critical information about the structural identity of the α-synuclein conformers that activate microglia and/or astrocytes and the molecular pathways involved...
February 21, 2024: Translational Neurodegeneration
https://read.qxmd.com/read/38368444/angiotensin-type-1-receptor-activation-promotes-neuronal-and-glial-alpha-synuclein-aggregation-and-transmission
#62
JOURNAL ARTICLE
Lucia Lage, Ana I Rodriguez-Perez, Begoña Villar-Cheda, Jose L Labandeira-Garcia, Antonio Dominguez-Meijide
The brain renin-angiotensin system (RAS) has been related to dopaminergic degeneration, and high expression of the angiotensin II (AngII) type 1 receptor (AT1) gene is a marker of the most vulnerable neurons in humans. However, it is unknown whether AngII/AT1 overactivation affects α-synuclein aggregation and transmission. In vitro, AngII/AT1 activation increased α-synuclein aggregation in dopaminergic neurons and microglial cells, which was related to AngII-induced NADPH-oxidase activation and intracellular calcium raising...
February 17, 2024: NPJ Parkinson's Disease
https://read.qxmd.com/read/38367511/new-insights-on-neurodegeneration-triggered-by-iron-accumulation-intersections-with-neutral-lipid-metabolism-ferroptosis-and-motor-impairment
#63
JOURNAL ARTICLE
Athina Maniscalchi, Oriana N Benzi Juncos, Melisa A Conde, Melania I Funk, María E Fermento, María M Facchinetti, Alejandro C Curino, Romina M Uranga, Natalia P Alza, Gabriela A Salvador
Brain iron accumulation constitutes a pathognomonic indicator in several neurodegenerative disorders. Metal accumulation associated with dopaminergic neuronal death has been documented in Parkinson's disease. Through the use of in vivo and in vitro models, we demonstrated that lipid dysregulation manifests as a neuronal and glial response during iron overload. In this study, we show that cholesterol content and triacylglycerol (TAG) hydrolysis were strongly elevated in mice midbrain. Lipid cacostasis was concomitant with the loss of dopaminergic neurons, astrogliosis and elevated expression of α-synuclein...
February 5, 2024: Redox Biology
https://read.qxmd.com/read/38366283/deciphering-m6a-signatures-in-hepatocellular-carcinoma-single-cell-insights-immune-landscape-and-the-protective-role-of-igfbp3
#64
JOURNAL ARTICLE
Shujia Chen, Jie Liu, Shuting Zhang, Lili Zhao, Jindong Zhang, Ping Han, Qian Zhang, Yao Liu, Fengmei Wang, Jia Li
RNA m6 methyladenosine (m6A) modifications impact tumor biology and immune processes, particularly in hepatocellular malignant tumors. Using a consensus clustering algorithm on 371 hepatocellular carcinoma (HCC) samples, we identified three m6A-modified subtypes and correlated them with positive tumor microenvironment (TME) markers for distinct immune phenotypes. Stratifying patients based on m6A scores revealed a low presentation group with better immune penetration, lower tumor mutation load, and increased expression of immune checkpoint markers like CTLA-4 and PD-1, suggesting enhanced responsiveness to immunization therapy...
February 16, 2024: Environmental Toxicology
https://read.qxmd.com/read/38355892/characterization-of-graded-6-hydroxydopamine-unilateral-lesion-in-medial-forebrain-bundle-of-mice
#65
JOURNAL ARTICLE
Juntao Cui, Di Zhao, Manman Xu, Zheheng Li, Junliang Qian, Ning Song, Jun Wang, Junxia Xie
Parkinson's disease (PD) is the second most common age-related neurodegenerative disease, with a progressive loss of dopaminergic cells and fibers. The purpose of this study was to use different doses of 6-hydroxydopamine (6-OHDA) injection into the medial forebrain bundle (MFB) of mice to mimic the different stages of the disease and to characterize in detail their motor and non-motor behavior, as well as neuropathological features in the nigrostriatal pathway. MFB were injected with 0.5 μg, 1 μg, 2 μg of 6-OHDA using a brain stereotaxic technique...
February 14, 2024: Scientific Reports
https://read.qxmd.com/read/38355786/molecular-profiling-of-the-hippocampus-of-children-with-autism-spectrum-disorder
#66
JOURNAL ARTICLE
Lindsay E Rexrode, Joshua Hartley, Kurt C Showmaker, Lavanya Challagundla, Michael W Vandewege, Brigitte E Martin, Estelle Blair, Ratna Bollavarapu, Rhenius B Antonyraj, Keauna Hilton, Alex Gardiner, Jake Valeri, Barbara Gisabella, Michael R Garrett, Theoharis C Theoharides, Harry Pantazopoulos
Several lines of evidence point to a key role of the hippocampus in Autism Spectrum Disorders (ASD). Altered hippocampal volume and deficits in memory for person and emotion related stimuli have been reported, along with enhanced ability for declarative memories. Mouse models have demonstrated a critical role of the hippocampus in social memory dysfunction, associated with ASD, together with decreased synaptic plasticity. Chondroitin sulfate proteoglycans (CSPGs), a family of extracellular matrix molecules, represent a potential key link between neurodevelopment, synaptic plasticity, and immune system signaling...
February 14, 2024: Molecular Psychiatry
https://read.qxmd.com/read/38351075/emergence-of-extracellular-vesicles-as-liquid-biopsy-for-neurological-disorders-boom-or-bust
#67
REVIEW
Ashish Kumar, Michael A Nader, Gagan Deep
Extracellular vesicles (EVs) have emerged as an attractive liquid biopsy approach in the diagnosis and prognosis of multiple diseases and disorders. The feasibility of enriching specific subpopulations of EVs from biofluids based on their unique surface markers has opened novel opportunities to gain molecular insight from various tissues and organs, including the brain. Over the past decade, EVs in bodily fluids have been extensively studied for biomarkers associated with various neurological disorders, such as Alzheimer's disease, Parkinson's disease, schizophrenia, bipolar disorder, major depressive disorders, substance use disorders, human immunodeficiency virus-associated neurocognitive disorder, and cancer/treatment-induced neurodegeneration...
February 13, 2024: Pharmacological Reviews
https://read.qxmd.com/read/38350506/mechanistic-study-of-the-anti-excitatory-amino-acid-toxicity-of-bushen-zhichan-decoction-for-parkinson-s-disease-based-on-the-transcriptional-regulation-of-eaat1-by-yy1
#68
JOURNAL ARTICLE
Leilei Liu, Xinyun Tian, Wentao Li
ETHNOPHARMACOLOGICAL RELEVANCE: Bushen Zhichan decoction (BSZCF) is derived from Liuwei Dihuang Pill, a famous Chinese herbal formula recorded in the book Key to Therapeutics of Children's Diseases. It has been widely used as a basic prescription for nourishing and tonifying the liver and kidneys to treat Parkinson's disease (PD), but its mechanism remains to be explored. AIM OF THE STUDY: BSZCF, a Chinese herbal formula comprising five herbs: Rehmannia glutinosa (Gaertn...
February 11, 2024: Journal of Ethnopharmacology
https://read.qxmd.com/read/38338925/what-can-inflammation-tell-us-about-therapeutic-strategies-for-parkinson-s-disease
#69
REVIEW
Jinsong Xue, Keju Tao, Weijia Wang, Xiaofei Wang
Parkinson's disease (PD) is a common neurodegenerative disorder with a complicated etiology and pathogenesis. α-Synuclein aggregation, dopaminergic (DA) neuron loss, mitochondrial injury, oxidative stress, and inflammation are involved in the process of PD. Neuroinflammation has been recognized as a key element in the initiation and progression of PD. In this review, we summarize the inflammatory response and pathogenic mechanisms of PD. Additionally, we describe the potential anti-inflammatory therapies, including nod-like receptor pyrin domain containing protein 3 (NLRP3) inflammasome inhibition, nuclear factor κB (NF-κB) inhibition, microglia inhibition, astrocyte inhibition, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibition, the peroxisome proliferator-activated receptor γ (PPARγ) agonist, targeting the mitogen-activated protein kinase (MAPK) pathway, targeting the adenosine monophosphate-activated protein kinase (AMPK)-dependent pathway, targeting α-synuclein, targeting miRNA, acupuncture, and exercise...
January 29, 2024: International Journal of Molecular Sciences
https://read.qxmd.com/read/38336311/the-vegfs-vegfrs-system-in-alzheimer-s-and-parkinson-s-diseases-pathophysiological-roles-and-therapeutic-implications
#70
REVIEW
Claudia Ceci, Pedro Miguel Lacal, Maria Luisa Barbaccia, Nicola Biagio Mercuri, Grazia Graziani, Ada Ledonne
The vascular endothelial growth factors (VEGFs) and their cognate receptors (VEGFRs), besides their well-known involvement in physiological angiogenesis/lymphangiogenesis and in diseases associated to pathological vessel formation, play multifaceted functions in the central nervous system (CNS). In addition to shaping brain development, by controlling cerebral vasculogenesis and regulating neurogenesis as well as astrocyte differentiation, the VEGFs/VEGFRs axis exerts essential functions in the adult brain both in physiological and pathological contexts...
February 7, 2024: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://read.qxmd.com/read/38336022/role-of-pyroptosis-in-the-pathogenesis-of-various-neurological-diseases
#71
REVIEW
Abiola Oladapo, Thomas Jackson, Jueliet Menolascino, Palsamy Periyasamy
Pyroptosis, an inflammatory programmed cell death process, has recently garnered significant attention due to its pivotal role in various neurological diseases. This review delves into the intricate molecular signaling pathways governing pyroptosis, encompassing both caspase-1 dependent and caspase-1 independent routes, while emphasizing the critical role played by the inflammasome machinery in initiating cell death. Notably, we explore the Nucleotide-binding domain leucine-rich repeat (NLR) containing protein family, the Absent in melanoma 2-like receptor family, and the Pyrin receptor family as essential activators of pyroptosis...
February 7, 2024: Brain, Behavior, and Immunity
https://read.qxmd.com/read/38334678/glymphatic-system-pathology-and-neuroinflammation-as-two-risk-factors-of-neurodegeneration
#72
REVIEW
Stanisław Szlufik, Kamila Kopeć, Stanisław Szleszkowski, Dariusz Koziorowski
The key to the effective treatment of neurodegenerative disorders is a thorough understanding of their pathomechanism. Neurodegeneration and neuroinflammation are mutually propelling brain processes. An impairment of glymphatic system function in neurodegeneration contributes to the progression of pathological processes. The question arises as to how neuroinflammation and the glymphatic system are related. This review highlights the direct and indirect influence of these two seemingly independent processes...
February 5, 2024: Cells
https://read.qxmd.com/read/38329129/blocking-il-6-signaling-prevents-astrocyte-induced-neurodegeneration-in-an-ipsc-based-model-of-parkinson-s-disease
#73
JOURNAL ARTICLE
Meritxell Pons-Espinal, Lucas Blasco-Agell, Irene Fernandez-Carasa, Pol Andrés-Benito, Angelique di Domenico, Yvonne Richaud-Patin, Valentina Baruffi, Laura Marruecos, Lluís Espinosa, Alicia Garrido, Eduardo Tolosa, Michael J Edel, Manel Juan Otero, José Luis Mosquera, Isidre Ferrer, Angel Raya, Antonella Consiglio
Parkinson's disease (PD) is a neurodegenerative disease associated with progressive death of midbrain dopamine (DAn) neurons in the substantia nigra (SN). Since it has been proposed that patients with PD exhibit an overall proinflammatory state, and since astrocytes are key mediators of the inflammation response in the brain, here we sought to address whether astrocyte-mediated inflammatory signaling could contribute to PD neuropathology. For this purpose, we generated astrocytes from induced pluripotent stem cells (iPSCs) representing patients with PD and healthy controls...
February 8, 2024: JCI Insight
https://read.qxmd.com/read/38323662/inorganic-polyphosphate-from-basic-research-to-diagnostic-and-therapeutic-opportunities-in-als-ftd
#74
JOURNAL ARTICLE
Polett Garcés, Armando Amaro, Martin Montecino, Brigitte van Zundert
Inorganic polyphosphate (polyP) is a simple, negatively charged biopolymer with chain lengths ranging from just a few to over a thousand ortho-phosphate (Pi) residues. polyP is detected in every cell type across all organisms in nature thus far analyzed. Despite its structural simplicity, polyP has been shown to play important roles in a remarkably broad spectrum of biological processes, including blood coagulation, bone mineralization and inflammation. Furthermore, polyP has been implicated in brain function and the neurodegenerative diseases amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), Alzheimer's disease and Parkinson's disease...
February 7, 2024: Biochemical Society Transactions
https://read.qxmd.com/read/38321352/mitochondria-endoplasmic-reticulum-contact-sites-mercs-a-new-axis-in-neuronal-degeneration-and-regeneration
#75
REVIEW
Vijaya Harini Sathyamurthy, Yoghalakshmi Nagarajan, Venkatachalam Deepa Parvathi
Mitochondria-Endoplasmic Reticulum Contact Sites (MERCS) are dynamic structures whose physiological interaction is vital to direct life and death of the cell. A bevy of tethering proteins, mitofusin-1/2 (Mfn-1/2), glucose-regulated protein-75 (Grp-75), voltage-dependent anion channel-1 (VDAC1), and dynamic-related protein-1 (Drp1), plays an integral role in establishing and regulating this intricate intracellular communication. Dysregulation of this interplay leads to various neurodegenerative disorders, like Alzheimer's disease (AD), Parkinson's disease (PD), stroke, traumatic brain injury (TBI), amyotrophic lateral sclerosis (ALS), and frontotemporal dementia (FTD)...
February 6, 2024: Molecular Neurobiology
https://read.qxmd.com/read/38315424/lrp10-and-%C3%AE-synuclein-transmission-in-lewy-body-diseases
#76
JOURNAL ARTICLE
Ana Carreras Mascaro, Martyna M Grochowska, Valerie Boumeester, Natasja F J Dits, Ece Naz Bilgiҫ, Guido J Breedveld, Leonie Vergouw, Frank Jan de Jong, Martin E van Royen, Vincenzo Bonifati, Wim Mandemakers
Autosomal dominant variants in LRP10 have been identified in patients with Lewy body diseases (LBDs), including Parkinson's disease (PD), Parkinson's disease-dementia (PDD), and dementia with Lewy bodies (DLB). Nevertheless, there is little mechanistic insight into the role of LRP10 in disease pathogenesis. In the brains of control individuals, LRP10 is typically expressed in non-neuronal cells like astrocytes and neurovasculature, but in idiopathic and genetic cases of PD, PDD, and DLB, it is also present in α-synuclein-positive neuronal Lewy bodies...
February 5, 2024: Cellular and Molecular Life Sciences: CMLS
https://read.qxmd.com/read/38307302/alpha-synuclein-pathology-is-associated-with-astrocyte-senescence-in-a-midbrain-organoid-model-of-familial-parkinson-s-disease
#77
JOURNAL ARTICLE
Mudiwa N Muwanigwa, Jennifer Modamio-Chamarro, Paul M A Antony, Gemma Gomez-Giro, Rejko Krüger, Silvia Bolognin, Jens C Schwamborn
Parkinson's disease (PD) is a complex, progressive neurodegenerative disease characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta in the midbrain. Despite extensive research efforts, the molecular and cellular changes that precede neurodegeneration in PD are poorly understood. To address this, here we describe the use of patient specific human midbrain organoids harboring the SNCA triplication to investigate mechanisms underlying dopaminergic degeneration. Our midbrain organoid model recapitulates key pathological hallmarks of PD, including the aggregation of α-synuclein and the progressive loss of dopaminergic neurons...
February 1, 2024: Molecular and Cellular Neurosciences
https://read.qxmd.com/read/38303529/vitamin-d-as-a-modulator-of-neuroinflammation-implications-for-brain-health
#78
JOURNAL ARTICLE
Sebastián García Menéndez, Walter Manucha
Neuroinflammation represents a critical immune response within the brain, playing a pivotal role in defense against injury and infection. However, when this response becomes chronic, it can contribute to the development of various neurodegenerative and psychiatric disorders. This bibliographic review delves into the role of vitamin D in modulating neuroinflammation and its implications for brain health, particularly in the context of neurological and psychiatric disorders. While vitamin D is traditionally associated with calcium homeostasis and bone health, it also exerts immunomodulatory and neuroprotective effects within the central nervous system...
February 1, 2024: Current Pharmaceutical Design
https://read.qxmd.com/read/38296953/phosphorylation-of-aqp4-by-lrrk2-r1441g-impairs-glymphatic-clearance-of-ifn%C3%AE-and-aggravates-dopaminergic-neurodegeneration
#79
JOURNAL ARTICLE
Heng Huang, Lishan Lin, Tengteng Wu, Cheng Wu, Leping Zhou, Ge Li, Fengjuan Su, Fengyin Liang, Wenyuan Guo, Weineng Chen, Qiuhong Jiang, Yalun Guan, Xuejiao Li, Pingyi Xu, Yu Zhang, Wanli Smith, Zhong Pei
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. The pro-inflammatory cytokine interferon (IFN) γ interacts with LRRK2 to induce neuroinflammation. Therefore, we examined the AQP4-dependent glymphatic system's role in IFNγ-mediated neuroinflammation in LRRK2-associated PD...
January 31, 2024: NPJ Parkinson's Disease
https://read.qxmd.com/read/38296489/neuroprotective-effect-of-gallic-acid-in-mice-with-rotenone-induced-neurodegeneration
#80
JOURNAL ARTICLE
Wachiryah Thong-Asa, Chatrung Wassana, Kunyarat Sukkasem, Pichcha Innoi, Montira Dechakul, Pattraporn Timda
We investigated the effect of gallic acid against neurodegenerative pathophysiology relevant to PD in mice with rotenone-induced toxicity. Forty male ICR mice were randomly divided into four groups: sham-veh, PD-veh (received subcutaneous injection with 2.5 mg/kg/48 h of rotenone); PD-Gal50; and PD-Gal100 (the latter two groups received subcutaneous injection with 2.5 mg/kg/48 h of rotenone and oral gavage with gallic acid 50 and 100 mg/kg/48 h, respectively). All treatments continued for 5 weeks with motor ability assessments once per week using hanging and rotarod tests...
February 1, 2024: Experimental Animals
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