The Role of Glymphatic System in Alzheimer’s and Parkinson’s Disease Pathogenesis

Biomedicines, Год журнала: 2022, Номер 10(9), С. 2261 - 2261

Опубликована: Сен. 13, 2022

Alzheimer's disease (AD) is the most common cause of neurodegenerative dementia, whilst Parkinson's (PD) a movement disorder. These two disorders share accumulation toxic proteins as pathological hallmark. The lack definitive disease-modifying treatments for these neurogenerative diseases has led to hypothesis new pathogenic mechanisms target and design potential therapeutic approaches. recent observation that glymphatic system supposed be responsible cerebrospinal fluid into brain clearance metabolic waste study its involvement in pathogenesis classic proteinopathies. Aquaporin-4 (AQP4), water channel located endfeet astrocyte membrane, considered primary driver system, defective AQP4-mediated drainage been linked objective present review body knowledge links AD PD other lifestyle factors such sleep deprivation exercise may influence function. We will also focus on neuroimaging approaches could identify marker detect changes.

Язык: Английский

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The glymphatic system and Amyotrophic lateral sclerosis

Progress in Neurobiology, Год журнала: 2024, Номер 234, С. 102571 - 102571

Опубликована: Янв. 22, 2024

Язык: Английский

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Neutrophil extracellular trap-mediated impairment of meningeal lymphatic drainage exacerbates secondary hydrocephalus after intraventricular hemorrhage

Theranostics, Год журнала: 2024, Номер 14(5), С. 1909 - 1938

Опубликована: Янв. 1, 2024

Rationale: Hydrocephalus is a substantial complication after intracerebral hemorrhage (ICH) or intraventricular (IVH) that leads to impaired cerebrospinal fluid (CSF) circulation.Recently, brain meningeal lymphatic vessels (mLVs) were shown serve as critical drainage pathways for CSF.Our previous studies indicated the degradation of neutrophil extracellular traps (NETs) ICH/IVH alleviates hydrocephalus.However, mechanisms by which NET exerts beneficial effects in hydrocephalus remain unclear.Methods: A mouse model following IVH was established infusing autologous blood into both wildtype and Cx3cr1 -/-mice.By studying features processes model, we investigated contribution mLVs NETs development progression secondary IVH.Results: This study observed widespread presence neutrophils, fibrin IVH, alleviated injury.Importantly, improved CSF enhancing recovery endothelial cells (LECs).Furthermore, our showed activated membrane protein CX3CR1 on LECs IVH.In contrast, repair promoted ameliorated knockdown -/-mice.Conclusion: Our findings participate injury contribute acute LEC thrombosis.CX3CR1 key molecule NET-induced damage thrombosis, mLV dysfunction exacerbates injury.NETs may be target preventing obstruction IVH.

Язык: Английский

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New perspectives on the glymphatic system and the relationship between glymphatic system and neurodegenerative diseases

Neurobiology of Disease, Год журнала: 2025, Номер 205, С. 106791 - 106791

Опубликована: Янв. 6, 2025

Neurodegenerative diseases (ND) are characterized by the accumulation of aggregated proteins. The glymphatic system, through its rapid exchange mechanisms between cerebrospinal fluid (CSF) and interstitial (ISF), facilitates movement metabolic substances within brain, serving functions akin to those peripheral lymphatic system. This emerging waste clearance mechanism offers a novel perspective on removal pathological in ND. article elucidates recent discoveries regarding system updates relevant concepts model. It discusses potential roles ND, including Alzheimer's disease (AD), Parkinson's (PD), multiple atrophy (MSA), proposes as therapeutic target for these conditions.

Язык: Английский

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Impaired Meningeal Lymphatics and Glymphatic Pathway in Patients with White Matter Hyperintensity

Advanced Science, Год журнала: 2024, Номер 11(26)

Опубликована: Май 5, 2024

Abstract White matter hyperintensity (WMH) represents a critical global medical concern linked to cognitive decline and dementia, yet its underlying mechanisms remain poorly understood. Here, humans are directly demonstrated that high WMH burden correlates with delayed drainage of meningeal lymphatic vessels (mLVs) glymphatic pathway. Additionally, longitudinal cohort study reveals dysfunction predicts progression. Next, in rat model WMH, the presence impaired lymphangiogenesis is confirmed, followed by elevated microglial activation white demyelination. Notably, enhancing through adeno‐associated virus delivery vascular endothelial growth factor‐C (VEGF‐C) mitigates gliosis Conversely, blocking mLVs VEGF‐C trap strategy exacerbates these changes. The findings highlight role pathway aggravating brain injury, providing potential novel for prevention treatment.

Язык: Английский

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Astrocytes in aging

Neuron, Год журнала: 2025, Номер 113(1), С. 109 - 126

Опубликована: Янв. 1, 2025

Язык: Английский

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Overview of the meningeal lymphatic vessels in aging and central nervous system disorders

Cell & Bioscience, Год журнала: 2022, Номер 12(1)

Опубликована: Дек. 17, 2022

Abstract In the aging process and central nervous system (CNS) diseases, functions of meningeal lymphatic vessels (MLVs) are impaired. Alterations in MLVs have been observed aging-related neurodegenerative brain tumors, even cerebrovascular disease. These findings reveal a new perspective on CNS disorders provide promising therapeutic target. Additionally, recent neuropathological studies shown that exchange soluble components between cerebrospinal fluid (CSF) interstitial (ISF) drain metabolites, cellular debris, misfolded proteins, immune cells from CSF into deep cervical lymph nodes (dCLNs), directly connecting with peripheral circulation. Impairment dysfunction lymphatics can lead to accumulation toxic proteins brain, exacerbating progression neurological disorders. However, for many causal relationship changes is not fully clear. Here, after brief historical retrospection, we review discoveries about hallmarks their roles as well potential targets treatment neurologic diseases.

Язык: Английский

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Brain Vascular Health in ALS Is Mediated through Motor Cortex Microvascular Integrity

Cells, Год журнала: 2023, Номер 12(6), С. 957 - 957

Опубликована: Март 21, 2023

Brain vascular health appears to be critical for preventing the development of amyotrophic lateral sclerosis (ALS) and slowing its progression. ALS patients often demonstrate cardiovascular risk factors commonly suffer from cerebrovascular disease, with evidence pathological alterations in their small cerebral blood vessels. Impaired brain has detrimental effects on motor neurons: endothelial growth factor levels are lowered ALS, which can compromise cell formation integrity blood–brain barrier. Increased turnover neurovascular unit cells precedes senescence, which, together pericyte alterations, further fosters failure toxic metabolite removal. We here provide a comprehensive overview pathogenesis impaired how novel magnetic resonance imaging techniques aid detection. In particular, we discuss patterns supply cortex number branches anterior middle arteries acting as marker resistance resilience against downstream events ALS. outline certain interventions adapted patient needs capabilities have potential mechanistically target microvasculature towards favorable patterns. Through this strategy, aim guide approaches management better understanding pathophysiology.

Язык: Английский

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Age-Related Alterations in Immune Function and Inflammation: Focus on Ischemic Stroke

Aging and Disease, Год журнала: 2023, Номер unknown

Опубликована: Янв. 1, 2023

The aging of the global population poses significant scientific challenges. Moreover, biological process is most risk factor for chronic illnesses; therefore, understanding molecular and cellular mechanisms underlying these aging-related challenges crucial extending healthy lifespan older individuals. Preventing brain remains a priority public health goal, integrative comprehensive analyses have revealed that immunosenescence potential cause age-related damage disease (e.g., stroke). Importantly, neuroinflammatory immune systems present two-way contact thus can affect each other. Emerging evidence supports numerous effects immunosenescence- inflammation-mediated immunity in neurologically injured brains. In this study, we briefly outline how alters pathophysiology transcriptional amplitude patients who experienced stroke then discuss system its components are affected by age after stroke. Finally, highlight emerging interventions with to slow down or reduce prevent onset.

Язык: Английский

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Molecular dynamics of amyloid-β transport in Alzheimer's disease: Exploring therapeutic plasma exchange with albumin replacement – Current insights and future perspectives

Neurología (English Edition), Год журнала: 2025, Номер 40(3), С. 306 - 328

Опубликована: Апрель 1, 2025

The complex process of amyloid-β (Aβ) transportation across the blood-brain and blood-cerebrospinal fluid barriers is crucial for preventing Aβ accumulation, which linked to dementia neurodegeneration. This review explores therapeutic plasma exchange with albumin replacement in Alzheimer's disease, based on dynamics between brain, plasma, cerebrospinal fluid. A comprehensive literature was conducted using PubMed/Medline, Cochrane Library, open databases (bioRxiv, MedRixv, preprint.org) up April 30, 2023. first search utilized following MeSH terms keywords: 'Plasma Exchange', 'Plasmapheresis', 'Therapeutic exchange', 'Apheresis', 'Aβ', 'p-tau', 'Total-tau', 'Alzheimer's disease', 'Cognitive dysfunction', 'neurodegenerative diseases', 'centrifugation', 'membranous', 'filtration' Title/Abstract, yielding 146 results. second 'Albumin', 'BBB', dementia', 'Nerve degeneration' resulted 125 additional articles analysis. Finally, a third 'Albumin structural domains', 'Albumin-Aβ interactions', 'Albumin-endothelial 'Post-Translational Modification' produced 193 results further review. Therapeutic shows potential as disease-modifying therapy dementia, specifically disease. Additionally, promising role supplementation cognitive improvement has attracted attention. However, clinical evidence supporting remains limited, necessitating research development mitigate adverse effects. deeper understanding molecular mechanisms essential. critical evaluation existing highlights importance balancing benefits associated risks, will guide application these treatments neurodegenerative diseases.

Язык: Английский

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