An update on the role of Hippo signaling pathway in ischemia-associated central nervous system diseases

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 162, P. 114619 - 114619

Published: March 31, 2023

The most frequent reason of morbidity and mortality in the world, cerebral ischemia sets off a chain molecular cellular pathologies that associated with some central nervous system (CNS) disorders mainly including ischemic stroke, Alzheimer's disease (AD), Parkinson's (PD), epilepsy other CNS diseases. In recent times, despite significant advancements treatment pathological processes underlying various neurological illnesses, effective therapeutic approaches are specifically targeted to minimizing damage such diseases remain absent. Hippo signaling pathway, characterized by enzyme linked reactions between MSTI/2, LAST1/2, YAP or TAZ proteins, controls cell division, survival, differentiation, as well being engaged variety biological activities, development transformation system. Recently, accumulating studies demonstrated pathway takes part AD, PD, etc., but not limited oxidative stress, inflammatory response, blood-brain barrier damage, mitochondrial disorders, neural cells death. Thus, it's crucial understand basis for determining potential new targets against ischemia-associated Here, we discuss latest advances deciphering highlight targeting treating

Language: Английский

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The Role of Oxygen Homeostasis and the HIF-1 Factor in the Development of Neurodegeneration

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(9), P. 4581 - 4581

Published: April 23, 2024

Understanding the molecular underpinnings of neurodegeneration processes is a pressing challenge for medicine and neurobiology. Alzheimer’s disease (AD) Parkinson’s (PD) represent most prevalent forms neurodegeneration. To date, substantial body experimental evidence has strongly implicated hypoxia in pathogenesis numerous neurological disorders, including AD, PD, other age-related neurodegenerative conditions. Hypoxia-inducible factor (HIF) transcription that triggers cell survival program conditions oxygen deprivation. The involvement HIF-1α presents complex sometimes contradictory picture. This review aims to elucidate current understanding interplay between development AD assess HIF-1 their pathogenesis, summarize promising therapeutic approaches centered on modulating activity complex.

Language: Английский

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Risk of Parkinson disease in stroke patients: A nationwide cohort study in South Korea

European Journal of Neurology, Journal Year: 2024, Volume and Issue: 31(4)

Published: Jan. 2, 2024

Abstract Background and purpose Previous studies have examined the risk of stroke in patients with Parkinson disease (PD), but incidence PD onset among its according to severity poststroke disabilities scarcely been investigated. This study aims determine whether is increased using a retrospective cohort large population‐based database. Methods We used data collected by Korean National Health Insurance Service from 2010 2018 307,361 380,917 sex‐ age‐matched individuals without uncover PD. Cox proportional hazards regression was calculate hazard ratio (HR) 95% confidence interval (CI), compared presence disability. Results During 4.31 years follow‐up, had 1.67 times higher (adjusted HR = 1.67, CI 1.57–1.78). The greater than those disabilities, even after adjustment for multiple covariates 1.72, 1.55–1.91; adjusted 1.66, 1.56–1.77, respectively). Conclusions Our demonstrated an patients. professionals need pay careful attention detecting movement disorders as clues diagnosing

Language: Английский

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Hypoxia Sensing and Responses in Parkinson’s Disease

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(3), P. 1759 - 1759

Published: Feb. 1, 2024

Parkinson’s disease (PD) is associated with various deficits in sensing and responding to reductions oxygen availability (hypoxia). Here we summarize the evidence pointing a central role of hypoxia PD, discuss relation dependence pathological hallmarks including mitochondrial dysfunction, dopaminergic vulnerability, alpha-synuclein-related pathology, highlight link cellular systemic sensing. We describe cases suggesting that may trigger Parkinsonian symptoms but also emphasize endogenous systems protect from can be harnessed PD. Finally, provide examples preclinical clinical research substantiating this potential.

Language: Английский

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HSP70 Modulators for the Correction of Cognitive, Mnemonic, and Behavioral Disorders After Prenatal Hypoxia

Biomedicines, Journal Year: 2025, Volume and Issue: 13(4), P. 982 - 982

Published: April 17, 2025

Background/Objectives: Prenatal hypoxia (PH) is a leading cause of nervous system disorders in early childhood and subsequently leads to decline the cognitive mnemonic functions central (such as memory impairment, reduced learning ability, information processing). It also increases anxiety risk brain adulthood. Compensatory–adaptive mechanisms mother–placenta–fetus system, which enhance fetus’s CNS resilience, are known, including activation endogenous neuroprotection response hypoxic injury through pharmacological modulation HSP70. Methods: To evaluate effect HSP70 modulators—Cerebrocurin, Angiolin, Tamoxifen, Glutaredoxin, Thiotriazoline, HSF-1 (heat shock factor 1 protein), well Mildronate Mexidol—on motor skills, exploratory behaviors, psycho-emotional activities, learning, memories offspring after PH. Experimental PH was induced by daily intraperitoneal injections sodium nitrite solution into pregnant female rats from 16th 21st day pregnancy at dose 50 mg/kg. The newborns received Angiolin (50 mg/kg), Thiotriazoline Mexidol (100 Cerebrocurin (150 µL/kg), L-arginine (200 Glutaredoxin µg/kg), or mg/kg) for 30 days. At month, were tested open field test, 2 months, they trained working spatial radial maze. Results: Modeling led persistent impairments activity, behavior, decrease cognitive–mnestic CNS. found that had most pronounced effects on indicators activity status 1-month-old animals They exhibited significant cognitive-enhancing memory-supporting during training evaluation skill retention maze 2-month-old Conclusions: first time, we obtained experimental data modulators following intrauterine hypoxia. Based results this study, identified agents promising neuroprotective perinatal

Language: Английский

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Association Between Serum α-Synuclein Levels and Neurocognitive Deficits in Patients with Obstructive Sleep Apnea: A Case-Control Study

Sleep Medicine, Journal Year: 2025, Volume and Issue: unknown, P. 106583 - 106583

Published: May 1, 2025

Language: Английский

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Glial Cultures Differentiated from iPSCs of Patients with PARK2-Associated Parkinson’s Disease Demonstrate a Pro-Inflammatory Shift and Reduced Response to TNFα Stimulation

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(3), P. 2000 - 2000

Published: Jan. 19, 2023

Parkinson's disease (PD) is the second most common neurodegenerative diseases characterized by progressive loss of midbrain dopaminergic neurons in substantia nigra. Mutations PARK2 gene are a frequent cause familial forms PD. Sustained chronic neuroinflammation central nervous system makes significant contribution to neurodegeneration events. In response inflammatory factors produced activated microglia, astrocytes change their transcriptional programs and secretion profiles, thus acting as immunocompetent cells. Here, we investigated iPSC-derived glial cell cultures obtained from healthy donors (HD) PD patients with mutations resting state upon stimulation TNFα. The non-stimulated glia demonstrated higher IL1B IL6 expression levels increased protein synthesis, while BDNF GDNF was down-regulated when compared that cells HDs. presence TNFα, all displayed multiplied genes encoding cytokines: TNFA, IL1B, IL6, well although responded TNFα less strongly than HD glia. Our results pro-inflammatory shift, suppression neuroprotective program, some depletion reactivity PARK2-deficient

Language: Английский

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Near-infrared enhanced organic se-doped carbon nitride quantum dots nanozymes as SOD/CAT mimics for anti-Parkinson via ROS-NF-κB-NLRP3 inflammasome axis

Chemical Engineering Journal, Journal Year: 2024, Volume and Issue: unknown, P. 156028 - 156028

Published: Sept. 1, 2024

Language: Английский

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The Hypoxia Response Pathway: A Potential Intervention Target in Parkinson's Disease?

Movement Disorders, Journal Year: 2023, Volume and Issue: 39(2), P. 273 - 293

Published: Dec. 23, 2023

Abstract Parkinson's disease (PD) is a progressive neurodegenerative disorder for which only symptomatic treatments are available. Both preclinical and clinical studies suggest that moderate hypoxia induces evolutionarily conserved adaptive mechanisms enhance neuronal viability survival. Therefore, targeting the response pathway might provide neuroprotection by ameliorating deleterious effects of mitochondrial dysfunction oxidative stress, underlie neurodegeneration in PD. Here, we review experimental regarding link between PD pathophysiology neurophysiological adaptations to hypoxia. We highlight mechanistic differences rescuing chronic short‐term improve resilience, termed “hypoxic conditioning”. Moreover, interpret these observations pharmacological pathway. Finally, discuss controversies with respect differential activation across spectrum, as well intervention dosing hypoxic conditioning potential harmful such interventions. recommend initial should focus on safety, physiological responses, conditioning, repurposing existing compounds. © 2023 International Parkinson Movement Disorder Society.

Language: Английский

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Nano-imaging agents for brain diseases: Environmentally responsive imaging and therapy

Nano Research, Journal Year: 2023, Volume and Issue: 16(12), P. 13134 - 13163

Published: Nov. 6, 2023

Language: Английский

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