Targetability of the neurovascular unit in inflammatory diseases of the central nervous system DOI

Brandon C. Smith,

Rachel A. Tinkey,

Benjamin C. Shaw

et al.

Immunological Reviews, Journal Year: 2022, Volume and Issue: 311(1), P. 39 - 49

Published: July 31, 2022

Summary The blood–brain barrier (BBB) is a selectively permeable separating the periphery from central nervous system (CNS). BBB restricts flow of most material into and out CNS, including many drugs that could be used as potent therapies. permeability modulated by several cells are collectively called neurovascular unit (NVU). NVU consists specialized CNS endothelial (ECs), pericytes, astrocytes, microglia, neurons. ECs maintain complex “seal” via tight junctions, forming BBB; breakdown these junctions leads to disruption. Pericytes control vascular within capillaries help basal lamina. Astrocytes much has moved beyond EC layer can form secondary under inflammatory conditions. Microglia survey border for noxious material. Neuronal activity also plays role in maintenance BBB. Since neurons all able modulate BBB, understating contributions each member will potentially uncover novel effective methods delivery neurotherapies CNS.

Language: Английский

Astrocytes in human central nervous system diseases: a frontier for new therapies DOI Creative Commons
Alexei Verkhratsky, Arthur M. Butt, Baoman Li

et al.

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Oct. 13, 2023

Astroglia are a broad class of neural parenchymal cells primarily dedicated to homoeostasis and defence the central nervous system (CNS). contribute pathophysiology all neurological neuropsychiatric disorders in ways that can be either beneficial or detrimental disorder outcome. Pathophysiological changes astroglia primary secondary result gain loss functions. respond external, non-cell autonomous signals associated with any form CNS pathology by undergoing complex variable their structure, molecular expression, function. In addition, internally driven, cell astroglial innate properties lead pathologies. Astroglial is complex, different pathophysiological states phenotypes context-specific vary disorder, disorder-stage, comorbidities, age, sex. Here, we classify into (i) reactive astrogliosis, (ii) atrophy function, (iii) degeneration death, (iv) astrocytopathies characterised aberrant forms drive disease. We review across spectrum human diseases disorders, including neurotrauma, stroke, neuroinfection, autoimmune attack epilepsy, as well neurodevelopmental, neurodegenerative, metabolic disorders. Characterising cellular mechanisms represents new frontier identify novel therapeutic strategies.

Language: Английский

Citations

159
Apolipoprotein E in lipid metabolism and neurodegenerative disease DOI Creative Commons
Linda Yang, Zachary M. March, Roxan A. Stephenson

et al.

Trends in Endocrinology and Metabolism, Journal Year: 2023, Volume and Issue: 34(8), P. 430 - 445

Published: June 24, 2023

Dysregulation of lipid metabolism has emerged as a central component many neurodegenerative diseases. Variants the transport protein, apolipoprotein E (APOE), modulate risk and resilience in several diseases including late-onset Alzheimer's disease (LOAD). Allelic variants gene, APOE, alter cells tissues have been broadly associated with other cellular systemic phenotypes. Targeting APOE-associated metabolic pathways may offer opportunities to disease-related phenotypes consequently, attenuate impart multiple We review molecular, cellular, tissue-level alterations that arise from different APOE isoforms. These changes could help elucidate mechanisms tune resilience.

Language: Английский

Citations

75
Blood–Brain Barrier Breakdown in Alzheimer’s Disease: Mechanisms and Targeted Strategies DOI Open Access
Amer E. Alkhalifa,

Nour F. Al-Ghraiybah,

Julia Odum

et al.

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

Citations

67
Cell type-specific roles of APOE4 in Alzheimer disease DOI
Jessica Blumenfeld, Oscar Yip, Min Joo Kim

et al.

Nature reviews. Neuroscience, Journal Year: 2024, Volume and Issue: 25(2), P. 91 - 110

Published: Jan. 8, 2024

Language: Английский

Citations

63
Astrocyte metabolism and signaling pathways in the CNS DOI Creative Commons
Yong-Mei Zhang, Yingbei Qi,

Ya-nan Gao

et al.

Frontiers in Neuroscience, Journal Year: 2023, Volume and Issue: 17

Published: Sept. 4, 2023

Astrocytes comprise half of the cells in central nervous system and play a critical role maintaining metabolic homeostasis. Metabolic dysfunction astrocytes has been indicated as primary cause neurological diseases, such depression, Alzheimer’s disease, epilepsy. Although functionalities are well known, their relationship to disorders is poorly understood. The ways which regulate metabolism glucose, amino acids, lipids have all implicated diseases. Metabolism also exhibited significant influence on neuron functionality brain’s neuro-network. In this review, we focused processes present astrocytes, most notably glucose pathway, fatty acid amino-acid pathway. For metabolism, glycolysis pentose-phosphate oxidative phosphorylation followed oxidation, ketone body sphingolipid metabolism. summarized neurotransmitter serine kynurenine pathways. This review will provide an overview functional changes astrocyte overall perspective current treatment therapy for disorders.

Language: Английский

Citations

45
Involvement of Astrocytes in the Formation, Maintenance, and Function of the Blood–Brain Barrier DOI Creative Commons
Gabriella Schiera, Carlo Maria Di Liegro,

Giuseppe Schirò

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(2), P. 150 - 150

Published: Jan. 12, 2024

The blood-brain barrier (BBB) is a fundamental structure that protects the composition of brain by determining which ions, metabolites, and nutrients are allowed to enter from blood or leave it towards circulation. BBB structurally composed layer capillary endothelial cells (BCECs) bound each other through tight junctions (TJs). However, its development as well maintenance properties controlled contact BCECs: pericytes, glial cells, even neurons themselves. Astrocytes seem, in particular, have very important role controlling most BBB. Here, we will focus on these latter since comprehension their roles physiology has been continuously expanding, including ability participate neurotransmission complex functions such learning memory. Accordingly, pathological conditions alter astrocytic can BBB's integrity, thus compromising many activities. In this review, also refer different kinds vitro models used study properties, evidencing modifications under conditions.

Language: Английский

Citations

37
Multifaceted roles of APOE in Alzheimer disease DOI
Rosemary J. Jackson, Bradley T. Hyman, Alberto Serrano‐Pozo

et al.

Nature Reviews Neurology, Journal Year: 2024, Volume and Issue: 20(8), P. 457 - 474

Published: June 21, 2024

Language: Английский

Citations

35
Revolutionizing Neurocare: Biomimetic Nanodelivery Via Cell Membranes DOI
Jun Liao, Lidong Gong,

Qingqiang Xu

et al.

Advanced Materials, Journal Year: 2024, Volume and Issue: 36(26)

Published: April 7, 2024

Abstract Brain disorders represent a significant challenge in medical science due to the formidable blood–brain barrier (BBB), which severely limits penetration of conventional therapeutics, hindering effective treatment strategies. This review delves into innovative realm biomimetic nanodelivery systems, including stem cell‐derived nanoghosts, tumor cell membrane‐coated nanoparticles, and erythrocyte membrane‐based carriers, highlighting their potential circumvent BBB's restrictions. By mimicking native properties, these nanocarriers emerge as promising solution for enhancing drug delivery brain, offering strategic advantage overcoming barrier's selective permeability. The unique benefits leveraging membranes from various sources is evaluated advanced technologies fabricating membrane‐encapsulated nanoparticles capable masquerading endogenous cells are examined. enables targeted broad spectrum therapeutic agents, ranging small molecule drugs proteins, thereby providing an approach neurocare. Further, contrasts capabilities limitations with traditional methods, underlining enable targeted, sustained, minimally invasive modalities. concluded perspective on clinical translation underscoring transformative impact landscape intractable brain diseases.

Language: Английский

Citations

30
Reactive Astrocytes and Emerging Roles in Central Nervous System (CNS) Disorders DOI
Shane A. Liddelow, Michelle L. Olsen, Michael V. Sofroniew

et al.

Cold Spring Harbor Perspectives in Biology, Journal Year: 2024, Volume and Issue: 16(7), P. a041356 - a041356

Published: Feb. 5, 2024

In addition to their many functions in the healthy central nervous system (CNS), astrocytes respond CNS damage and disease through a process called "reactivity." Recent evidence reveals that astrocyte reactivity is heterogeneous spectrum of potential changes occur context-specific manner. These are determined by diverse signaling events vary not only with nature severity different insults but also location CNS, genetic predispositions, age, potentially "molecular memory" previous events. Astrocyte can be associated both essential beneficial as well harmful effects. The available information rapidly expanding much has been learned about molecular diversity reactivity. Emerging functional associations point toward roles for determining outcome disorders.

Language: Английский

Citations

16
The barrier and interface mechanisms of the brain barrier, and brain drug delivery DOI Creative Commons
Shanshan Zhang, Lin Gan, Fengye Cao

et al.

Brain Research Bulletin, Journal Year: 2022, Volume and Issue: 190, P. 69 - 83

Published: Sept. 23, 2022

Three different barriers are formed between the cerebrovascular and brain parenchyma: blood-brain barrier (BBB), blood-cerebrospinal fluid (BCSFB), cerebrospinal fluid-brain (CBB). The BBB is main regulator of blood central nervous system (CNS) material exchange. semipermeable nature limits passage larger molecules hydrophilic small molecules, Food Drug Administration (FDA)-approved drugs for CNS have been generally limited to lipid-soluble molecules. Although complexity affects drug delivery, understanding composition function can provide a platform development new methods delivery. This review summarizes classification barrier, role basic structures BBB, transport, destruction mechanisms BBB; discusses advantages disadvantages delivery prospects future strategies.

Language: Английский

Citations

58