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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Evaluating the robustness of DTI-ALPS in clinical context: a meta-analytic parallel on Alzheimer’s and Parkinson’s diseases

Scientific Reports, Journal Year: 2024, Volume and Issue: 14(1)

Published: Nov. 2, 2024

In recent years, the glymphatic system has received increasing attention due to its possible implications in biological mechanisms associated with neurodegeneration. field of human brain mapping, this led development diffusion tensor image analysis along perivascular space (DTI-ALPS) index. While index been repeatedly used investigate differences between neurodegenerative disorders and healthy controls, a comprehensive evaluation stability across multiple measurements different is still missing. study, we perform Bayesian meta-analysis aiming assess consistency DTI-ALPS results previously reported for 12 studies on Parkinson's disease 11 Alzheimer's disease. We also evaluated if measured value can quantitatively inform diagnostic process, allowing disambiguation these two disorders. Our results, expressed terms Bayes' Factor values, confirmed that consistent measuring functioning subjects patients both (Log10(BF10) = 30) 10). Moreover, showed be compare directly, therefore providing first proof concept supporting reliability taking into consideration neuroimaging measurement process. study underscores potential advancing our understanding pathologies enhancing clinical diagnostics.

Language: Английский

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Glymphatic defect in isolated REM sleep behavior disorder is associated with phenoconversion to Parkinson's disease

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 15, 2025

Abstract Isolated rapid eye movement (REM) sleep behavior disorder (iRBD) is characterized by the loss of muscle atonia and abnormal, often violent, movements vocalizations during REM sleep. It strongest prodromal marker for progression to synucleinopathies such as dementia with Lewy bodies (DLB) Parkinson’s disease (PD). iRBD individuals already show brain changes consistent manifest synucleinopathies, but their mechanisms remain poorly understood. The glymphatic system involved in clearance waste products its defect has been associated a higher likelihood pathological burden neurodegeneration. presence dysfunction revealed neuroimaging association uninvestigated, including potential predict conversion toward distinct trajectories synucleinopathies. We analyzed diffusion-weighted imaging data from large international multicentric cohort polysomnography-confirmed healthy controls. used diffusion tensor along perivascular space assess function derived index based on diffusivity occurring within masks placed associative projection fibers adjacent lateral ventricles. was compared between groups correlated motor cognitive features. Cox regression models assessed relationship PD, DLB or remaining disease-free. Our analyses included 250 participants (mean age 66.5 ± 6.8 years; 87% men) 178 controls (65.7 81% men). There significantly reduced Among 224 followed longitudinally (6.1 years, 1-16 years), 65 developed neurodegenerative disease. converters exhibited lower non-converters. Lower risk phenoconversion towards PD over time disease-free (hazard ratio = 2.43, 95% CI 1.13-5.25, P 0.012). This study reports predicting underscoring utility identifying at-risk individuals.

Language: Английский

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Brain Glycogen—Its Metabolic Role in Neuronal Health and Neurological Disorders—An Extensive Narrative Review

Metabolites, Journal Year: 2025, Volume and Issue: 15(2), P. 128 - 128

Published: Feb. 13, 2025

Background: Brain glycogen is imperative for neuronal health, as it supports energy demands and metabolic processes. This review examines the pathways involved in storage utilization central nervous system, emphasizing their role both physiology pathology. It explores how alterations metabolism contribute to neurological disorders, including neurodegenerative diseases, epilepsy, conditions while highlighting bidirectional interaction between neurons glia maintaining brain homeostasis. Methods: A comprehensive search of articles published 2015 2025 was conducted using following databases: ScienceDirect, Scopus, Wiley, Web Science, Medline, PubMed. The selection relevant studies based on focus its conditions, with that did not meet inclusion criteria being excluded. Results: processes are subject rigorous regulation by astrocyte-neuron interactions, thereby ensuring homeostasis availability. dysregulation mobilization has been implicated development synaptic dysfunction, excitotoxicity, neurodegeneration a variety disorders. For instance, aberrant accumulation diseases such Lafora disease associated severe neurodegeneration, impaired shown exacerbate deficits Alzheimer's epilepsy. Conclusions: Targeting represents promising approach therapeutic intervention However, translation these strategies human models remains challenging, particularly regard long-term safety specificity glycogen-targeted therapies.

Language: Английский

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Aerobic exercise improves clearance of amyloid-β via the glymphatic system in a mouse model of Alzheimer's Disease

Brain Research Bulletin, Journal Year: 2025, Volume and Issue: 222, P. 111263 - 111263

Published: Feb. 18, 2025

Language: Английский

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Perivascular space and white matter hyperintensities in Alzheimer’s disease: associations with disease progression and cognitive function

Alzheimer s Research & Therapy, Journal Year: 2025, Volume and Issue: 17(1)

Published: March 18, 2025

Alzheimer's disease (AD) is the leading cause of dementia, characterized by accumulation amyloid-beta (Aβ) and neurofibrillary tangles. Recent studies emphasize role vascular factors, including glymphatic system, in AD pathogenesis, particularly Aβ clearance. The diffusion tensor image analysis along perivascular space (DTI-ALPS; ALPS-Index) has emerged as a novel, non-invasive method to evaluate system vivo, showing insufficiency AD. This study aimed investigate alterations function individuals with versus healthy controls (HC), explore its association Aβ, cerebrovascular (CVD), white matter hyperintensities (WMH), cognitive function. DTI MRI data from three independent cohorts (ActiGliA: n = 16, Controls 18; DELCODE: 54, 67; ADNI: 43, 49) were used (PVS) integrity; potential biomarker for activity. DTI-Along Perivascular Space technique was measure water PVS providing an index assess efficiency system's waste clearance WMH load quantified FLAIR using lesion segmentation tool. We WMHs volume within our defined region interest (ROI) excluded participants any avoid confounding ALPS-Index. Associations cerebrospinal fluid (CSF) hallmark biomarkers, performance (MMSE) clinical severity (CDR) assessed. patients had significantly lower ALPS-Index vs. AD: mean 1.22, SD 0.12; Controls: 1.36, 0.14, p 0.004; 1.26, 0.18; 1.34, 0.2, 0.035; 1.08, 0.24; 1.19, 0.13, 0.008). associated CSF concentration, number MMSE CDR. WMH, found ROIs correlated negatively highlights DTI-ALPS-Index dysfunction It underscores importance considering factors pathogenesis diagnosis ROI could disturbances inaccurate indices.

Language: Английский

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Association of glymphatic system function with peripheral inflammation and motor symptoms in Parkinson’s disease

npj Parkinson s Disease, Journal Year: 2025, Volume and Issue: 11(1)

Published: March 28, 2025

Growing evidence highlights the roles of glymphatic system and peripheral inflammation in Parkinson's disease (PD). We evaluated their interrelationship potential mechanisms contributing to motor symptoms using DTI-ALPS inflammatory markers (leukocyte, lymphocyte, neutrophil counts, neutrophil-to-lymphocyte ratio [NLR], platelet-to-lymphocyte [PLR]) 134 PD patients (52 tremor-dominant [TD], 62 postural instability gait difficulty [PIGD]) 81 healthy controls (HC, 33 with markers). exhibited lower than HC (1.43 ± 0.19 vs. 1.52 0.21, p = 0.001). was negatively correlated NLR, PLR, neutrophils (all < 0.05) PIGD (β –0.043, 0.048), positively lymphocytes TD 0.105, 0.034). mediated relationship between (NLR neutrophils) MDS-UPDRS III score PD. Overall, dysfunction correlates may mediate effects on PD, distinct profiles PIGD.

Language: Английский

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Molecular and metabolic effects of chronic stress on health, aging and carcinogenesis

Biopolymers and Cell, Journal Year: 2025, Volume and Issue: 41(1), P. 23 - 31

Published: April 14, 2025

Language: Английский

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Reactive astrocyte-derived exosomes enhance intracranial lymphatic drainage in mice after intracranial hemorrhage

Fluids and Barriers of the CNS, Journal Year: 2025, Volume and Issue: 22(1)

Published: April 14, 2025

Language: Английский

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The selective butyrylcholinesterase inhibitor UW‐MD‐95 shows symptomatic and neuroprotective effects in a pharmacological mouse model of Alzheimer's disease

CNS Neuroscience & Therapeutics, Journal Year: 2024, Volume and Issue: 30(6)

Published: June 1, 2024

Alzheimer's disease (AD) is a devastating dementia characterized by extracellular amyloid-β (Aβ) protein aggregates and intracellular tau deposition. Clinically available drugs mainly target acetylcholinesterase (AChE) indirectly sustain cholinergic neuronal tonus. Butyrylcholinesterase (BChE) also controls acetylcholine (ACh) turnover involved in the formation of Aß senile plaques. UW-MD-95 novel carbamate-based compound acting as potent pseudo-irreversible BChE inhibitor, with high selectivity versus AChE, showing promising protective potentials AD.

Language: Английский

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