Peripheral Inflammation and Insulin Resistance: Their Impact on Blood–Brain Barrier Integrity and Glia Activation in Alzheimer’s Disease DOI Open Access
Teresa Ponce-López

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(9), P. 4209 - 4209

Published: April 29, 2025

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, memory impairment, and synaptic dysfunction. The accumulation of amyloid beta (Aβ) plaques hyperphosphorylated tau protein leads to neuronal dysfunction, neuroinflammation, glial cell activation. Emerging evidence suggests that peripheral insulin resistance chronic inflammation, often associated with type 2 diabetes (T2D) obesity, promote increased proinflammatory cytokines, oxidative stress, immune infiltration. These conditions further damage the blood-brain barrier (BBB) integrity neurotoxicity This induces neuroinflammation impaired signaling, reducing glucose metabolism exacerbating Aβ hyperphosphorylation. Indeed, epidemiological studies have linked T2D obesity an risk developing AD, reinforcing connection between metabolic disorders neurodegeneration. review explores relationships resistance, BBB highlighting their role in activation exacerbation AD pathology.

Language: Английский

Advancing neurological disorders therapies: Organic nanoparticles as a key to blood-brain barrier penetration DOI Creative Commons
Zahra Razavi,

Seyed Sina Alizadeh,

F. S. Razavi

et al.

International Journal of Pharmaceutics, Journal Year: 2025, Volume and Issue: 670, P. 125186 - 125186

Published: Jan. 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.

Language: Английский

Citations

12
Crossing the blood–brain barrier: emerging therapeutic strategies for neurological disease DOI

Josephine H Pedder,

Adam M. Sonabend,

Michael D Cearns

et al.

The Lancet Neurology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

4
Exploring the microbiota-gut-brain axis: impact on brain structure and function DOI Creative Commons

Lidya K. Yassin,

Mohammed M. Nakhal,

Alreem Alderei

et al.

Frontiers in Neuroanatomy, Journal Year: 2025, Volume and Issue: 19

Published: Feb. 12, 2025

The microbiota-gut-brain axis (MGBA) plays a significant role in the maintenance of brain structure and function. MGBA serves as conduit between CNS ENS, facilitating communication emotional cognitive centers via diverse pathways. In initial stages this review, we will examine way how affects neurogenesis, neuronal dendritic morphology, axonal myelination, microglia structure, blood barrier (BBB) permeability, synaptic structure. Furthermore, review potential mechanistic pathways neuroplasticity through influence. short-chain fatty acids (SCFAs) play pivotal MGBA, where they can modify BBB. We therefore discuss SCFAs influence microglia, neuronal, astrocyte function, well their disorders such Alzheimer’s disease (AD), Parkinson’s (PD). Subsequently, technical strategies employed to study interactions, including using germ-free (GF) animals, probiotics, fecal microbiota transplantation (FMT), antibiotics-induced dysbiosis. Finally, particular bacterial strains affect By gaining deeper understanding it may be possible facilitate research into microbial-based pharmacological interventions therapeutic for neurological diseases.

Language: Английский

Citations

3
The Underlying Neurobiological Mechanisms of Psychosis: Focus on Neurotransmission Dysregulation, Neuroinflammation, Oxidative Stress, and Mitochondrial Dysfunction DOI Creative Commons

Neha S. Rawani,

Allen W. Chan, Serdar Dursun

et al.

Antioxidants, Journal Year: 2024, Volume and Issue: 13(6), P. 709 - 709

Published: June 12, 2024

Psychosis, defined as a set of symptoms that results in distorted sense reality, is observed several psychiatric disorders addition to schizophrenia. This paper reviews the literature relevant underlying neurobiology psychosis. The dopamine hypothesis has been major influence study neurochemistry psychosis and development antipsychotic drugs. However, it became clear early on other factors must be involved dysfunction In current review, reported how these factors, namely dysregulation neurotransmitters [dopamine, serotonin, glutamate, γ-aminobutyric acid (GABA)], neuroinflammation, glia (microglia, astrocytes, oligodendrocytes), hypothalamic–pituitary–adrenal axis, gut microbiome, oxidative stress, mitochondrial contribute interact with one another. Research increased knowledge complexity psychotic disorders. Potential new pharmacotherapies, including combinations drugs (with pre- probiotics some cases) affecting mentioned above, have suggested. Similarly, putative biomarkers, particularly those related immune system, proposed. Future research both pharmacotherapy biomarkers will require better-designed studies conducted an all stages consider confounders such sex differences comorbidity.

Language: Английский

Citations

16
Glial Cells as Key Regulators in Neuroinflammatory Mechanisms Associated with Multiple Sclerosis DOI Open Access

Styliani Theophanous,

Irene Sargiannidou, Kleopas A. Kleopa

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(17), P. 9588 - 9588

Published: Sept. 4, 2024

Even though several highly effective treatments have been developed for multiple sclerosis (MS), the underlying pathological mechanisms and drivers of disease not fully elucidated. In recent years, there has a growing interest in studying neuroinflammation context glial cell involvement as is increasing evidence their central role progression. Although communication proper function underlies brain homeostasis maintenance, effects an MS remain complex controversial. this review, we aim to provide overview contribution cells, oligodendrocytes, astrocytes, microglia pathology during both activation orchestration inflammatory mechanisms, well synergistic repair restoration function. Additionally, discuss how understanding may new therapeutic targets either limit progression or facilitate repair.

Language: Английский

Citations

9
Neurovascular unit, neuroinflammation and neurodegeneration markers in brain disorders DOI Creative Commons
Duraisamy Kempuraj,

Kirk D. Dourvetakis,

Jessica R. Cohen

et al.

Frontiers in Cellular Neuroscience, Journal Year: 2024, Volume and Issue: 18

Published: Oct. 25, 2024

Neurovascular unit (NVU) inflammation via activation of glial cells and neuronal damage plays a critical role in neurodegenerative diseases. Though the exact mechanism disease pathogenesis is not understood, certain biomarkers provide valuable insight into pathogenesis, severity, progression therapeutic efficacy. These markers can be used to assess pathophysiological status brain including neurons, astrocytes, microglia, oligodendrocytes, specialized microvascular endothelial cells, pericytes, NVU, blood-brain barrier (BBB) disruption. Damage or derangements tight junction (TJ), adherens (AdJ), gap (GJ) components BBB lead increased permeability neuroinflammation various disorders disorders. Thus, neuroinflammatory evaluated blood, cerebrospinal fluid (CSF), tissues determine neurological progression, responsiveness. Chronic common age-related Alzheimer's (AD), Parkinson's (PD), dementia. Neurotrauma/traumatic injury (TBI) also leads acute chronic responses. The expression some may altered many years even decades before onset In this review, we discuss neuroinflammation, neurodegeneration associated with disorders, especially those neurovascular pathologies. CSF, tissues. Neurofilament light (NfL), ubiquitin C-terminal hydrolase-L1 (UCHL1), fibrillary acidic protein (GFAP), Ionized calcium-binding adaptor molecule 1 (Iba-1), transmembrane 119 (TMEM119), aquaporin, endothelin-1, platelet-derived growth factor receptor beta (PDGFRβ) are important markers. Recent BBB-on-a-chip modeling offers promising potential for providing an in-depth understanding neurotherapeutics. Integration these clinical practice could potentially enhance early diagnosis, monitor improve outcomes.

Language: Английский

Citations

8
Advances in the Study of Necroptosis in Vascular Dementia: Focus on Blood–Brain Barrier and Neuroinflammation DOI Creative Commons

Yuemin Qiu,

Lin Cheng,

Yinyi Xiong

et al.

CNS Neuroscience & Therapeutics, Journal Year: 2025, Volume and Issue: 31(2)

Published: Feb. 1, 2025

ABSTRACT Background Vascular dementia (VaD) includes a group of brain disorders that are characterized by cerebrovascular pathology.Neuroinflammation, disruption the blood–brain barrier (BBB) permeability, white matter lesions, and neuronal loss all significant pathological manifestations VaD play key role in disease progression. Necroptosis, also known asprogrammed necrosis, is mode programmed cell death distinct from apoptosis closely associated with ischemic injury neurodegenerative diseases. Recent studies have shown necroptosis exacerbates BBB destruction, activates neuroinflammation, promotes loss, severely affects prognosis. Results Conclusions In this review, we outline roles its molecular mechanisms process VaD, particular focus on modulating neuroinflammation exacerbating permeability elaborate regulatory centrally involved cells mediated tumor necrosis factor‐α VaD. We analyze possibility specific strategy targeting would help inhibit destruction With necroptosis, study delved into impact changes prognosis to provide new treatment ideas.

Language: Английский

Citations

1
Molecular Motors in Blood–Brain Barrier Maintenance by Astrocytes DOI Creative Commons
Ana Filipa Sobral, Inês Costa, Vanessa Teixeira

et al.

Brain Sciences, Journal Year: 2025, Volume and Issue: 15(3), P. 279 - 279

Published: March 6, 2025

The blood–brain barrier (BBB) comprises distinct cell types, including endothelial cells, pericytes, and astrocytes, is essential for central nervous system (CNS) homeostasis by selectively regulating molecular transport maintaining integrity. In particular, astrocytes are BBB function, as they maintain integrity through their end-feet, which form a physical biochemical interface that enhances function selectivity. Moreover, secrete growth factors like vascular factor (VEGF) transforming factor-beta (TGF-β), regulate tight junction (TJ) proteins (e.g., claudins occludins) crucial limiting paracellular permeability. Molecular motors kinesins, dynein, myosins these astrocyte functions. By facilitating vesicular trafficking protein transport, various functions, of junctional to support integrity, the proper mitochondria localization within processes efficient energy supply, polarized distribution aquaporin (AQP)-4 at end-feet water across BBB, modulation neuroinflammatory responses. myosin modulate actomyosin dynamics process outgrowth, adhesion, migration, morphology, functional roles. Thus, motor dysregulation in can compromise increasing risk neurodegeneration. This review explores complex interplay between homeostasis, represents an attractive but poorly explored area research.

Language: Английский

Citations

1
Brain Metabolism in Health and Neurodegeneration: The Interplay Among Neurons and Astrocytes DOI Creative Commons
Polina Shichkova, Jay S. Coggan, Henry Markram

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(20), P. 1714 - 1714

Published: Oct. 17, 2024

The regulation of energy in the brain has garnered substantial attention recent years due to its significant implications various disorders and aging. brain's metabolism is a dynamic tightly regulated network that balances demand supply by engaging complementary molecular pathways. crosstalk among these pathways enables system switch preferred fuel source based on substrate availability, activity levels, cell state-related factors such as redox balance. Brain production relies multi-cellular cooperation continuously supplied from blood limited internal stores. Astrocytes, which interface with neurons vessels, play crucial role coordinating metabolic activity, their dysfunction can have detrimental effects health. This review characterizes major substrates (glucose, lactate, glycogen, ketones lipids) astrocyte health, focusing developments field.

Language: Английский

Citations

6
Role of the transcription factor NRF2 in maintaining the integrity of the Blood-Brain Barrier DOI Creative Commons

Eduardo Cazalla,

Antonio Cuadrado, Ángel J. García‐Yagüe

et al.

Fluids and Barriers of the CNS, Journal Year: 2024, Volume and Issue: 21(1)

Published: Nov. 21, 2024

The Blood-Brain Barrier (BBB) is a complex and dynamic interface that regulates the exchange of molecules cells between blood central nervous system. It undergoes structural functional throughout oxidative stress inflammation, which may compromise its integrity contribute to pathogenesis neurodegenerative diseases. Maintaining BBB utmost importance in preventing wide range neurological disorders. NRF2 main transcription factor cellular redox balance inflammation-related gene expression. has also demonstrated potential role regulating tight junction contributing inhibition ECM remodeling, by reducing expression several metalloprotease family members involved maintaining function. Overall, we review current insights on addressing protection against effects dysfunction, discuss involvement maintenance different neuropathological diseases, as well as, some activators have been used vitro vivo animal models for barrier dysfunction. Thus, emerging evidence suggests upregulation target genes could suppress stress, neuroinflammation, restore integrity, increase protection.

Language: Английский

Citations

4