Advancing neurological disorders therapies: Organic nanoparticles as a key to blood-brain barrier penetration

International Journal of Pharmaceutics, Год журнала: 2025, Номер 670, С. 125186 - 125186

Опубликована: Янв. 8, 2025

The blood-brain barrier (BBB) plays a vital role in protecting the central nervous system (CNS) by preventing entry of harmful pathogens from bloodstream. However, this also presents significant obstacle when it comes to delivering drugs for treatment neurodegenerative diseases and brain cancer. Recent breakthroughs nanotechnology have paved way creation wide range nanoparticles (NPs) that can serve as carriers diagnosis therapy. Regarding their promising properties, organic NPs potential be used effective drug delivery across BBB based on recent advancements. These remarkable ability penetrate using various mechanisms. This review offers comprehensive examination intricate structure distinct properties BBB, emphasizing its crucial function preserving balance regulating transport ions molecules. disruption conditions such stroke, Alzheimer's disease, Parkinson's disease highlights importance developing creative approaches drugs. Through encapsulation therapeutic molecules precise targeting processes vasculature, NP formulations present hopeful strategy improve BBB. We explore changes pathological investigate factors affect successful into brain. In addition, we most systems associated with shown positive results treating ischemic disorders. opens up new possibilities nanotechnology-based therapies cerebral diseases.

Язык: Английский

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Understanding glucose metabolism and insulin action at the blood–brain barrier: Implications for brain health and neurodegenerative diseases

Acta Physiologica, Год журнала: 2025, Номер 241(2)

Опубликована: Янв. 16, 2025

The blood-brain barrier (BBB) is a highly selective, semipermeable critical for maintaining brain homeostasis. BBB regulates the transport of essential nutrients, hormones, and signaling molecules between bloodstream central nervous system (CNS), while simultaneously protecting from potentially harmful substances pathogens. This selective permeability ensures that nourished shielded toxins. An exception to this are regions, such as hypothalamus circumventricular organs, which irrigated by fenestrated capillaries, allowing rapid direct response various blood components. We overview metabolic functions BBB, with an emphasis on impact altered glucose metabolism insulin in pathogenesis neurodegenerative diseases. Notably, endothelial cells constituting exhibit distinct characteristics, primarily generating ATP through aerobic glycolysis. occurs despite their exposure abundant oxygen bloodstream, typically supports oxidative phosphorylation. effects astrocytes, form glial limitans component show marked sexual dimorphism. nutrient sensing hypothalamus, along signaling, systemic metabolism. Insulin modifies regulating expression tight junction proteins, angiogenesis, vascular remodeling, well modulating flow brain. disruptions particularly evident diseases, Alzheimer's disease Parkinson's disease, where breakdown accelerates cognitive decline. review highlights role normal functionality investigates how these pathways contribute onset progression

Язык: Английский

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Neuroglial decline defines cognitive ageing

Ageing & Longevity, Год журнала: 2025, Номер 1.2025, С. 6 - 21

Опубликована: Янв. 17, 2025

Neuroglia of the central nervous system, represented by astroglia, oligodendroglia and microglia, are fundamental for life-long support homeostasis, plasticity defence neural tissue. In particular neuroglial cells contribute to cognitive reserve, which defines neurological outcome both physiological pathological ageing. Physiological ageing is accompanied with structural functional decline neuroglia. particular, astrocytes undergo morphological atrophy asthenia compromises their vital functions such as glutamate clearance, K+ buffering synaptic support. Old oligodendrocytes lose myelination capacity, results in thinning myelin sheath white matter. Finally, associated accumulation dystrophic microglia limits neuroprotection. Age-dependent impedes contributes impairment, increases vulnerability system neurodegeneration. Life style changes positively impact on structure function this improving longevity. Keywords: ageing; longevity; neuroglia, oligodendroglia; oligodendroglial precursor cells;

Язык: Английский

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The Dual Role of Amyloid Beta-Peptide in Oxidative Stress and Inflammation: Unveiling Their Connections in Alzheimer’s Disease Etiopathology

Antioxidants, Год журнала: 2024, Номер 13(10), С. 1208 - 1208

Опубликована: Окт. 8, 2024

Alzheimer's disease (AD) is a progressive neurodegenerative disease, and it currently the seventh leading cause of death worldwide. It characterized by extracellular aggregation amyloid β-peptide (Aβ) into oligomers fibrils that synaptotoxicity neuronal death. Aβ exhibits dual role in promoting oxidative stress inflammation. This review aims to unravel intricate connection between these processes their contribution AD progression. The delves AD, focusing on involvement metals, mitochondrial dysfunction, biomolecule oxidation. distinct yet overlapping concept nitro-oxidative also discussed, detailing roles nitric oxide, perturbations, cumulative impact production neurotoxicity. Inflammation examined through astroglia microglia function, elucidating response within brain. blood-brain barrier oligodendrocytes are considered context pathophysiology. We current diagnostic methodologies emerging therapeutic strategies aimed at mitigating inflammation, thereby offering potential treatments for halting or slowing comprehensive synthesis underscores pivotal bridging advancing our understanding informing future research treatment paradigms.

Язык: Английский

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Dysregulation of Ion Channels and Transporters and Blood-Brain Barrier Dysfunction in Alzheimer’s Disease and Vascular Dementia

Aging and Disease, Год журнала: 2024, Номер unknown

Опубликована: Янв. 1, 2024

The blood-brain barrier (BBB) plays a critical role in maintaining ion and fluid homeostasis, essential for brain metabolism neuronal function. Regulation of nutrient, water, transport across the BBB is tightly controlled by specialized transporters channels located within its unique cellular components. These dynamic processes not only influence BBB’s structure but also impact vital signaling mechanisms, optimal Disruption ion, pH, balance at associated with pathology has been implicated various neurological conditions, including stroke, epilepsy, trauma, neurodegenerative diseases such as Alzheimer’s disease (AD). However, knowledge gaps exist regarding dysregulation on function dementias. Several factors contribute to this gap: complex nature these historical research focus mechanisms technical challenges studying in vivo models lack efficient vitro dementia models. This review provides an overview current roles poses specific questions: 1) How are expression activity key altered AD vascular (VaD); 2) Do changes dysfunction progression; 3) Can restoring mitigate improve clinical outcomes. Addressing will provide greater insight into disorders.

Язык: Английский

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Noradrenergic system in the pathogenesis of age-dependent neurodegeneration

Ageing & Longevity, Год журнала: 2025, Номер 1.2025, С. 28 - 34

Опубликована: Янв. 28, 2025

Ageing is a key factor in the development of cognitive decline and neurodegeneration, including Alzheimer’s disease (AD), most common form dementia diagnosed. In 2023 US Federal Drug Administration (FDA) approved new drug (Lecanemab, Leqembi) to treat AD that very moderately slows down early-stage (van Dyck et al., 2023). Donanemab (Kisunla, Eli Lilley), acting similarly lecanemab, was by FDA 2024 US, but not yet European Medicines Agency (EMA) EU. The mechanism action both these monoclonal antibodies similar aducanumab (Aduhelm), conditionally for 2021 (but subsequently discontinued producer), on reducing β-amyloid deposits (Sevigny 2016; van However, trials all revealed significant adverse events (brain swelling or brain bleeding); hence treatment neurodegeneration general remains an important unmet medical need, affecting millions people worldwide. Here I discuss role noradrenergic system innervating spinal cord, consisting nucleus locus coeruleus (LC), which appears be vulnerable structure central nervous (CNS) ageing-related factors, leading early LC demise impairments. Therefore, propose understanding noradrenaline cells, particular astrocytes, homeostasis-providing exhibit high density adrenergic receptors, future strategy develop drugs mitigate decline. Keywords: ageing; noradrenaline; adrenoceptors; coeruleus; neuroglia, astrocytes

Язык: Английский

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Trace metals and astrocytes physiology and pathophysiology

Cell Calcium, Год журнала: 2024, Номер 118, С. 102843 - 102843

Опубликована: Янв. 4, 2024

Язык: Английский

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The spatial landscape of glial pathology and T-cell response in Parkinson’s disease substantia nigra

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Янв. 9, 2024

Abstract Parkinson’s Disease (PD) is a progressive neurodegenerative disease that leads to debilitating movement disorders and often dementia. Recent evidence, including identification of specific peripheral T-cell receptor sequences, indicates the adaptive immune response associated with pathogenesis. However, properties T-cells in brain regions where neurons degenerate are not well characterized. We have analyzed identities interactions PD post-mortem tissue using single nucleus RNA sequencing, spatial transcriptomics sequencing. found substantia nigra donors exhibit CD8+ resident memory phenotype, increased clonal expansion, altered relationships astrocytes, myeloid cells, endothelial cells. also describe regional differences astrocytic responses neurodegeneration. Our findings nominate potential molecular cellular candidates allow deeper understanding pathophysiology neurodegeneration PD. Together, our work represents major transcriptional resource for fields

Язык: Английский

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The pathways and the mechanisms by which Cryptococcus enters the brain

Mycology&#58 An International Journal on Fungal Biology, Год журнала: 2024, Номер 15(3), С. 345 - 359

Опубликована: Фев. 14, 2024

Generally, Cryptococcus initially infects the respiratory tract, but can spread, eventually crossing blood-brain barrier (BBB) and causing meningitis or meningoencephalitis. Specifically, invades vascular endothelial cells of BBB, from which it enters brain. The main mechanisms through crosses BBB are transcellular traversal, paracellular pathway, via Trojan horse. In this paper, by were explained in detail. addition to pathways entry brain, paper presents a discussion on some rare cryptococcal infections provides insights for future research directions.

Язык: Английский

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Nanoparticle Interactions with the Blood Brain Barrier: Insights from Drosophila and Implications for Human Astrocyte Targeted Therapies

Neurochemical Research, Год журнала: 2025, Номер 50(1)

Опубликована: Янв. 20, 2025

Язык: Английский

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