Endocannabinoid signaling in the central nervous system DOI

César E. Martinez Ramirez,

Gonzalo Ruiz‐Pérez, Todd M. Stollenwerk

и другие.

Glia, Год журнала: 2022, Номер 71(1), С. 5 - 35

Опубликована: Окт. 29, 2022

It is hard to overestimate the influence of endocannabinoid signaling (ECS) system on central nervous (CNS) function. In 40 years since cannabinoids were found trigger specific cell cascades, studies ECS continue cause amazement, surprise, and confusion! CB1 cannabinoid receptors are expressed widely in CNS regulate cell-cell communication via effects release both neurotransmitters gliotransmitters. CB2 difficult detect but seem "punch above their weight" as compounds targeting these have significant inflammatory state behavior. Positive negative allosteric modulators for been identified examined preclinical studies. Concentrations ligands, N-arachidonoylethanolamine 2-arachidonoylglycerol (2-AG), regulated by a combination enzymatic synthesis degradation inhibitors processes available making way into clinical trials. Importantly, regulates many essential brain functions, including regulation reward, anxiety, inflammation, motor control, cellular development. While field cusp discoveries providing impactful therapeutic insights disorders, there still much be learned about this remarkable versatile modulatory system.

Язык: Английский

Transdermal delivery of resveratrol loaded solid lipid nanoparticle as a microneedle patch: a novel approach for the treatment of Parkinson’s disease DOI

Akshay Bandiwadekar,

Jobin Jose, Gopika Gopan

и другие.

Drug Delivery and Translational Research, Год журнала: 2024, Номер unknown

Опубликована: Июнь 29, 2024

Язык: Английский

Процитировано

11

Betulinic acid protects against lipopolysaccharide and ferrous sulfate-induced oxidative stress, ferroptosis, apoptosis, and neuroinflammation signaling relevant to Parkinson's Disease DOI
Shivam Kumar Pandey,

Anjuman Nanda,

Avtar Singh Gautam

и другие.

Free Radical Biology and Medicine, Год журнала: 2025, Номер unknown

Опубликована: Апрель 1, 2025

Язык: Английский

Процитировано

1

The NRF2-Dependent Transcriptional Regulation of Antioxidant Defense Pathways: Relevance for Cell Type-Specific Vulnerability to Neurodegeneration and Therapeutic Intervention DOI Creative Commons
Stephanie M. Boas, Kathlene L. Joyce, Rita M. Cowell

и другие.

Antioxidants, Год журнала: 2021, Номер 11(1), С. 8 - 8

Опубликована: Дек. 21, 2021

Oxidative stress has been implicated in the etiology and pathobiology of various neurodegenerative diseases. At baseline, cells nervous system have capability to regulate genes for antioxidant defenses by engaging nuclear factor erythroid 2 (NFE2/NRF)-dependent transcriptional mechanisms, a number strategies proposed activate these pathways promote neuroprotection. Here, we briefly review biology transcription factors NFE2/NRF family brain provide evidence differential cellular localization members system. We then discuss findings context oxidative observed two diseases, Parkinson’s disease (PD) amyotrophic lateral sclerosis (ALS), present current activating NFE2/NRF-dependent transcription. Based on expression restricted populations neurons glia, propose that, when designing engage neuroprotection, relative contributions neuronal non-neuronal cell types overall state tissue should be considered, as well which greatest intrinsic capacity producing enzymes.

Язык: Английский

Процитировано

46

Neurons and Glia Interplay in α-Synucleinopathies DOI Open Access
Panagiota Mavroeidi, Maria Xilouri

International Journal of Molecular Sciences, Год журнала: 2021, Номер 22(9), С. 4994 - 4994

Опубликована: Май 8, 2021

Accumulation of the neuronal presynaptic protein alpha-synuclein within proteinaceous inclusions represents key histophathological hallmark a spectrum neurodegenerative disorders, referred to by umbrella term a-synucleinopathies. Even though is expressed predominantly in neurons, pathological aggregates are also found glial cells brain. In Parkinson's disease and dementia with Lewy bodies, accumulates mainly neurons forming bodies neurites, whereas multiple system atrophy, mostly cytoplasmic oligodendrocytes. addition, astrogliosis microgliosis synucleinopathy brains, both astrocytes microglia internalize contribute spread pathology. The mechanisms underlying accumulation that under physiological conditions express low non-detectable levels an area intense research. Undoubtedly, presence aggregated can disrupt function general neurodegeneration through numerous pathways. Herein, we summarize current knowledge on role glia, highlighting contribution neuron-glia connectome initiation progression, which may represent potential therapeutic target for

Язык: Английский

Процитировано

44

Polarization of Microglia and Its Therapeutic Potential in Sepsis DOI Open Access

Léo Victor Grimaldi de Castro,

Cassiano Felippe Gonçalves-de-Albuquerque, Adriana Ribeiro Silva

и другие.

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(9), С. 4925 - 4925

Опубликована: Апрель 28, 2022

Sepsis is a life-threatening organ dysfunction caused by dysregulated host response to infection, leaving the inflammation process without proper resolution, leading tissue damage and possibly sequelae. The central nervous system (CNS) one of first regions affected peripheral sepsis, exposing neurons an environment oxidative stress, triggering neuronal apoptosis. Sepsis-associated encephalopathy (SAE) most frequent sepsis-associated dysfunction, with symptoms such as deliriums, seizures, coma, linked increased mortality, morbidity, cognitive disability. However, current therapy does not avoid those patients' symptoms, evidencing search for more optimal approach. Herein we focus on microglia prominent therapeutic target due its multiple functions maintaining CNS homeostasis polarizing capabilities, stimulating resolving neuroinflammation depending stimuli. Microglia polarization studies involving nerve cell preservation in diseases or aggravated neuroinflammation, but potential overlooked. We highlight peroxisome proliferator-activated receptor gamma (PPARγ) neuroprotective properties, role interaction nuclear factor-κB (NF-κB) mitogen-activated kinases (MAPK), making PPARγ molecular sepsis-related come.

Язык: Английский

Процитировано

30

Recent progress and applications of small molecule inhibitors of Keap1–Nrf2 axis for neurodegenerative diseases DOI
Jing Wang,

Yu Cao,

Lu Yang

и другие.

European Journal of Medicinal Chemistry, Год журнала: 2023, Номер 264, С. 115998 - 115998

Опубликована: Ноя. 29, 2023

Язык: Английский

Процитировано

19

JE-133 Suppresses LPS-Induced Neuroinflammation Associated with the Regulation of JAK/STAT and Nrf2 Signaling Pathways DOI

Ling-Xue Tao,

Weichen Yu,

Ziyi Liu

и другие.

ACS Chemical Neuroscience, Год журнала: 2024, Номер 15(2), С. 258 - 267

Опубликована: Янв. 5, 2024

Neuroinflammation plays an important role in the pathogenesis of neurodegenerative diseases, and interrupting microglial-mediated neuroinflammation has been suggested as a promising strategy to delay or prevent progression neurodegeneration. In this study, we investigated effects JE-133, optically active isochroman-2H-chromene conjugate containing 1,3-disubstituted isochroman unit, on lipopolysaccharide (LPS)-induced microglial underlying mechanisms both vitro vivo. First, JE-133 treatment decreased LPS-induced overproduction interleukin-1 beta (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), nitrite, nitric oxide synthase (iNOS) BV2 cells. Further study revealed that downregulated phosphorylation level JAK/STAT upregulated protein Nrf2/HO-1 LPS-stimulated cells verified directly bound Keap1 by pull-down assay. Next, administration also inhibited vivo, indicated reduced CD11b overexpressed mRNA pro-inflammatory cytokine TNF-α hippocampus LPS-injected mice. Moreover, regulative pathways were Taken together, our for first time reports exhibits inhibitory against which might be associated with simultaneous regulation Nrf2 pathways. Our findings may provide clues discovery effective drug leads/candidates neuroinflammation-associated

Язык: Английский

Процитировано

7

The potential role of brain renin‐angiotensin system in the neuropathology of Parkinson disease: Friend, foe or turncoat? DOI Creative Commons
Zainah Al‐Qahtani, Hayder M. Al‐kuraishy, Ali I. Al‐Gareeb

и другие.

Journal of Cellular and Molecular Medicine, Год журнала: 2024, Номер 28(12)

Опубликована: Июнь 1, 2024

Abstract Parkinson disease (PD) is one of the most common neurodegenerative diseases brain. Of note, brain renin‐angiotensin system (RAS) intricate in PD neuropathology through modulation oxidative stress, mitochondrial dysfunction and neuroinflammation. Therefore, RAS by angiotensin receptor blockers (ARBs) angiotensin‐converting enzyme inhibitors (ACEIs) may be effective reducing risk neuropathology. It has been shown that all components including peptides enzymes are present different areas. Brain plays a critical role regulation memory cognitive function, controlling central blood pressure. However, exaggerated implicated pathogenesis PD. Two well‐known pathways recognized including; classical pathway which mainly mediated AngII/AT1R detrimental effects. Conversely, non‐classical mostly ACE2/Ang1‐7/MASR AngII/AT2R beneficial effects against Exaggerated affects viability dopaminergic neurons. fundamental mechanism was not fully elucidated. Consequently, purpose this review to disclose mechanistic In addition, we try revise how ACEIs ARBs can developed for therapeutics

Язык: Английский

Процитировано

7

NRF2 Activation and Downstream Effects: Focus on Parkinson’s Disease and Brain Angiotensin DOI Creative Commons
Juan A. Parga, Ana I. Rodríguez‐Pérez, María García-Garrote

и другие.

Antioxidants, Год журнала: 2021, Номер 10(11), С. 1649 - 1649

Опубликована: Окт. 20, 2021

Reactive oxygen species (ROS) are signalling molecules used to regulate cellular metabolism and homeostasis. However, excessive ROS production causes oxidative stress, one of the main mechanisms associated with origin progression neurodegenerative disorders such as Parkinson’s disease. NRF2 (Nuclear Factor-Erythroid 2 Like 2) is a transcription factor that orchestrates response stress. The regulation has been shown be promising strategy modulate neurodegeneration pathway affected in patients this disease, activation neuroprotective effects preclinical models, demonstrating therapeutic potential pathway. In review, we highlight recent advances regarding NRF2, including effect Angiotensin II an endogenous molecule able stress dopaminergic neurons. genes regulated downstream activation, special focus on Kruppel Factor 9 (KLF9) factor, provide clues about involved process well future approaches.

Язык: Английский

Процитировано

34

Exendin-4 and linagliptin attenuate neuroinflammation in a mouse model of Parkinson′s disease DOI
Haiyang Yu, Tong Sun, Zhen Wang

и другие.

Neural Regeneration Research, Год журнала: 2022, Номер 0(0), С. 0 - 0

Опубликована: Янв. 1, 2022

Use of glucagon-like peptide-1 receptor agonist or dipeptidyl peptidase 4 inhibitor has been shown to lower the incidence Parkinson's disease in patients with diabetes mellitus. Therefore, using these two treatments may help treat disease. To further investigate mechanisms action compounds, we established a model by treating mice 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and then subcutaneously injected them exendin-4 linagliptin. We found that both linagliptin reversed motor dysfunction, glial activation, dopaminergic neuronal death this model. In addition, induced microglial polarization anti-inflammatory M2 phenotype reduced pro-inflammatory cytokine secretion. Moreover, vitro experiments showed treatment inhibited activation nucleotide-binding oligomerization domain- leucine-rich-repeat- pyrin-domain-containing 3/caspase-1/interleukin-1β pathway subsequent pyroptosis decreasing production reactive oxygen species. These findings suggest exert neuroprotective effects attenuating neuroinflammation through regulation mouse 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. drugs serve as novel for

Язык: Английский

Процитировано

27