Blood–Brain Barrier Breakdown in Alzheimer’s Disease: Mechanisms and Targeted Strategies

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(22), P. 16288 - 16288

Published: Nov. 14, 2023

The blood-brain barrier (BBB) is a unique and selective feature of the central nervous system's vasculature. BBB dysfunction has been observed as an early sign Alzheimer's Disease (AD) before onset dementia or neurodegeneration. intricate relationship between pathogenesis AD, especially in context neurovascular coupling overlap pathophysiology neurodegenerative cerebrovascular diseases, underscores urgency to understand BBB's role more deeply. Preserving restoring function emerges potentially promising strategy for mitigating progression severity AD. Molecular genetic changes, such isoform ε4 apolipoprotein E (ApoEε4), significant risk factor promoter dysfunction, have shown mediate disruption. Additionally, receptors transporters like low-density lipoprotein receptor-related protein 1 (LRP1), P-glycoprotein (P-gp), receptor advanced glycation end products (RAGEs) implicated AD's pathogenesis. In this comprehensive review, we endeavor shed light on pathogenic therapeutic connections AD BBB. We also delve into latest developments pioneering strategies targeting interventions, addressing its potential carrier. By providing integrative perspective, anticipate paving way future research treatments focused exploiting therapy.

Language: Английский

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High fried food consumption impacts anxiety and depression due to lipid metabolism disturbance and neuroinflammation

Proceedings of the National Academy of Sciences, Journal Year: 2023, Volume and Issue: 120(18)

Published: April 24, 2023

Western dietary patterns have been unfavorably linked with mental health. However, the long-term effects of habitual fried food consumption on anxiety and depression underlying mechanisms remain unclear. Our population-based study 140,728 people revealed that frequent consumption, especially potato is strongly associated 12% 7% higher risk depression, respectively. The associations were more pronounced among male younger consumers. Consistently, exposure to acrylamide, a representative processing contaminant in products, exacerbates scototaxis thigmotaxis, further impairs exploration ability sociality adult zebrafish, showing anxiety- depressive-like behaviors. Moreover, treatment acrylamide significantly down-regulates gene expression tjp2a related permeability blood-brain barrier. Multiomics analysis showed chronic induces cerebral lipid metabolism disturbance neuroinflammation. PPAR signaling pathway mediates acrylamide-induced disorder brain zebrafish. Especially, dysregulates sphingolipid phospholipid metabolism, which plays important roles development symptoms. In addition, promotes peroxidation oxidation stress, participate Acrylamide dramatically increases markers peroxidation, including (±)5-HETE, 11(S)-HETE, 5-oxoETE, up-regulates proinflammatory mediators such as (±)12-HETE 14(S)-HDHA, indicating elevated inflammatory status after acrylamide. Together, these results both epidemiologically mechanistically provide strong evidence unravel mechanism acrylamide-triggered highlight significance reducing for

Language: Английский

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Immunotherapy in glioblastoma treatment: Current state and future prospects

World Journal of Clinical Oncology, Journal Year: 2023, Volume and Issue: 14(4), P. 138 - 159

Published: April 20, 2023

Glioblastoma remains as the most common and aggressive malignant brain tumor, standing with a poor prognosis treatment prospective. Despite standard care, such surgical resection chemoradiation, median survival rates are low. In this regard, immunotherapeutic strategies aim to become more attractive for glioblastoma, considering its recent advances approaches. review, we provide an overview of current status progress in immunotherapy going through fundamental knowledge on immune targeting promising strategies, Chimeric antigen receptor T-Cell therapy, checkpoint inhibitors, cytokine-based treatment, oncolytic virus vaccine-based techniques. At last, it is discussed innovative methods overcome diverse challenges, future perspectives area.

Language: Английский

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Exosomes as therapeutic and drug delivery vehicle for neurodegenerative diseases

Journal of Nanobiotechnology, Journal Year: 2024, Volume and Issue: 22(1)

Published: Aug. 2, 2024

Abstract Neurodegenerative disorders are complex, progressive, and life-threatening. They cause mortality disability for millions of people worldwide. Appropriate treatment neurodegenerative diseases (NDs) is still clinically lacking due to the presence blood-brain barrier (BBB). Developing an effective transport system that can cross BBB enhance therapeutic effect neuroprotective agents has been a major challenge NDs. Exosomes endogenous nano-sized vesicles naturally carry biomolecular cargoes. Many studies have indicated exosome content, particularly microRNAs (miRNAs), possess biological activities by targeting several signaling pathways involved in apoptosis, inflammation, autophagy, oxidative stress. Exosome content influence cellular function healthy or pathological ways. Furthermore, since exosomes reflect features parental cells, their cargoes offer opportunities early diagnosis intervention diseases. unique characteristics make them ideal delivering drugs directly brain. These include ability pass through BBB, biocompatibility, stability, innate properties. This review emphasizes role alleviating NDs discusses associated molecular mechanisms. exosomes, making promising natural transporter various medications brain combat NDs, also discussed.

Language: Английский

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Microglial activation states and their implications for Alzheimer's Disease

The Journal of Prevention of Alzheimer s Disease, Journal Year: 2025, Volume and Issue: 12(1), P. 100013 - 100013

Published: Jan. 1, 2025

Alzheimer's Disease (AD) is a chronic neurodegenerative disorder characterized by the accumulation of toxic amyloid-beta (Aβ) plaques and neurofibrillary tangles (NFTs) tau protein in brain. Microglia, key immune cells central nervous system, play an important role AD development progression, primarily through their responses to Aβ NFTs. Initially, microglia can clear Aβ, but AD, activation overwhelms protective mechanisms, leading sustained neuroinflammation that enhances plaque toxicity, setting off damaging cycle affects neurons, astrocytes, cerebral vasculature, other microglia. Current treatments have been largely ineffective, though emerging immunotherapies focusing on removal show promise, often overlook neuroinflammation. Activated display complex range phenotypes be broadly broken into pro- or anti-inflammatory states, although this dichotomy does not describe significant overlap between states. strongly induce inflammatory activity, triggering production reactive oxygen species, cytokines (e.g., TNF-α, IL-1β, IL-6), synapse engulfment, blood-brain barrier compromise, impaired clearance. These processes contribute neural tissue loss, manifesting as cognitive decline such executive function memory. Conversely, exerts neuroprotective effects suppressing pathways releasing neurotrophic factors aid neuron repair protection. Induction states may offer dual therapeutic approach address both AD. This suggests potential strategies modulate microglial phenotypes, aiming restore functions mitigate disease progression simultaneously targeting inflammation pathology.

Language: Английский

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Recent Advances in Nanoenzymes Based Therapies for Glioblastoma: Overcoming Barriers and Enhancing Targeted Treatment

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 24, 2025

Abstract Glioblastoma multiforme (GBM) is a highly aggressive and malignant brain tumor originating from glial cells, characterized by high recurrence rates poor patient prognosis. The heterogeneity complex biology of GBM, coupled with the protective nature blood–brain barrier (BBB), significantly limit efficacy traditional therapies. rapid development nanoenzyme technology presents promising therapeutic paradigm for rational targeted treatment GBM. In this review, underlying mechanisms GBM pathogenesis are comprehensively discussed, emphasizing impact BBB on strategies. Recent advances in nanoenzyme‐based approaches therapy explored, highlighting how these nanoenzymes enhance various modalities through their multifunctional capabilities potential precise drug delivery. Finally, challenges prospects translating laboratory research to clinical application, including issues stability, targeting efficiency, safety, regulatory hurdles critically analyzed. By providing thorough understanding both opportunities obstacles associated therapies, future directions aimed be informed contribute more effective treatments

Language: Английский

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The Crucial Role of the Blood–Brain Barrier in Neurodegenerative Diseases: Mechanisms of Disruption and Therapeutic Implications

Journal of Clinical Medicine, Journal Year: 2025, Volume and Issue: 14(2), P. 386 - 386

Published: Jan. 9, 2025

The blood-brain barrier (BBB) is a crucial structure that maintains brain homeostasis by regulating the entry of molecules and cells from bloodstream into central nervous system (CNS). Neurodegenerative diseases such as Alzheimer's Parkinson's disease, well ischemic stroke, compromise integrity BBB. This leads to increased permeability infiltration harmful substances, thereby accelerating neurodegeneration. In this review, we explore mechanisms underlying BBB disruption, including oxidative stress, neuroinflammation, vascular dysfunction, loss tight junction integrity, in patients with neurodegenerative diseases. We discuss how breakdown contributes neurotoxicity, abnormal accumulation pathological proteins, all which exacerbate neuronal damage facilitate disease progression. Furthermore, potential therapeutic strategies aimed at preserving or restoring function, anti-inflammatory treatments, antioxidant therapies, approaches enhance integrity. Given role neurodegeneration, maintaining its represents promising approach slow prevent progression

Language: Английский

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Niosomes for nose-to-brain delivery: A non-invasive versatile carrier system for drug delivery in neurodegenerative diseases

Journal of Drug Delivery Science and Technology, Journal Year: 2023, Volume and Issue: 89, P. 105007 - 105007

Published: Sept. 28, 2023

Language: Английский

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Vulnerability of the Hippocampus to Insults: Links to Blood–Brain Barrier Dysfunction

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(4), P. 1991 - 1991

Published: Feb. 6, 2024

The hippocampus is a critical brain substrate for learning and memory; events that harm the can seriously impair mental behavioral functioning. Hippocampal pathophysiologies have been identified as potential causes effects of remarkably diverse array medical diseases, psychological disorders, environmental sources damage. It may be more vulnerable than other areas to insults are related these conditions. One purpose this review assess vulnerability most prevalent types in multiple biomedical domains (i.e., neuroactive pathogens, neurotoxins, neurological conditions, trauma, aging, neurodegenerative disease, acquired injury, health endocrine developmental disabilities, nutrition) evaluate whether affect first prominently compared loci. A second consider role hippocampal blood–brain barrier (BBB) breakdown either causing or worsening harmful each insult. Recent research suggests BBB fragile also prone disruption transport mechanisms act maintain internal milieu. Moreover, compromised could factor common many different insults. Our analysis indicates parts brain, developing interventions protect help prevent ameliorate on memory cognition.

Language: Английский

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Phenolic Compounds of Therapeutic Interest in Neuroprotection

Journal of Xenobiotics, Journal Year: 2024, Volume and Issue: 14(1), P. 227 - 246

Published: Feb. 6, 2024

The number of elderly people is projected to double in the next 50 years worldwide, resulting an increased prevalence neurodegenerative diseases. Aging causes changes brain tissue homeostasis, thus contributing development disorders. Current treatments are not entirely effective, so alternative or adjuvant agents being actively sought. Antioxidant properties phenolic compounds particular interest for diseases whose psychopathological mechanisms strongly rely on oxidative stress at level. Moreover, display other advantages such as permeability blood–brain barrier (BBB) and interesting molecular that we reviewed this work. We began by briefly outlining physiopathology understand result irreversible damage, then provided overall classification would be addressed later. vitro vivo studies, well some clinical trials which neuroprotective were demonstrated models different amyotrophic lateral sclerosis (ALS), Alzheimer’s disease (AD), Parkinson’s (PD), ischemia, traumatic injury (TBI).

Language: Английский

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