The neurovascular unit (NVU) is involved in the pathological changes in Alzheimer's disease (AD). The NVU is a structural and functional complex that maintains microenvironmental homeostasis and metabolic balance in the central nervous system. As one of the most important components of the NVU, microglia not only induce blood-brain barrier breakdown by promoting neuroinflammation, the infiltration of peripheral white blood cells and oxidative stress but also mediate neurovascular uncoupling by inducing mitochondrial dysfunction in neurons, abnormal contraction of cerebral vessels, and pericyte loss in AD. In addition, microglia-mediated dysfunction of cellular components in the NVU, such as astrocytes and pericytes, can destroy the integrity of the NVU and lead to NVU impairment. Therefore, we review the mechanisms of microglia-mediated NVU dysfunction in AD. Furthermore, existing therapeutic advancements aimed at restoring the function of microglia and the NVU in AD are discussed. Finally, we predict the role of pericytes in microglia-mediated NVU dysfunction in AD is the hotspot in the future.
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http://dx.doi.org/10.3233/JAD-221064 | DOI Listing |
Acta Pharm Sin B
December 2024
Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry and Sichuan Province, West China School of Pharmacy, Mental Health Center and National Chengdu Center for Safety Evaluation of Drugs, West China Hospital, Sichuan University, Chengdu 610041, China.
The neurovascular unit (NVU) is highly responsible for cerebral homeostasis and its dysfunction emerges as a critical contributor to Alzheimer's disease (AD) pathology. Hence, rescuing NVU dysfunction might be a viable approach to AD treatments. Here, we fabricated a self-regulated muti-functional nano-modulator (siR/PIO@RP) that can intelligently navigate to damaged blood-brain barrier and release therapeutical cargoes for synergetic AD therapy.
View Article and Find Full Text PDFExp Neurol
January 2025
Department of Anesthesiology and Pain Medicine, Anesthesia and Pain Research Institute, Yonsei University College of Medicine, Seoul, Republic of Korea. Electronic address:
Perioperative neurocognitive disorders (PNDs) refer to a wide spectrum of cognitive impairment persisting days to even after a year postoperative with significant morbidity and mortality. However, despite much efforts involving perioperative managements, PNDs are still prevalent with no standard preventative and therapeutic strategy. To overcome PNDs, a better understanding of pathophysiology of PNDs is crucial and a large number of studies have proven that immune-inflammatory responses from surgical stress are involved in the abnormal activation of the hypothalamic-pituitary-adrenal (HPA) axis and destabilization of neurovascular unit (NVU) that lead to PNDs.
View Article and Find Full Text PDFBMC Chem
January 2025
Pharmaceutical Chemistry Department, Faculty of Pharmacy, Nile Valley University (NVU), El Fayoum, 63518, Egypt.
Coronavirus disease 2019 (COVID-19), an extremely contagious illness, has posed enormous challenges to healthcare systems around the world. Although the evidence on COVID-19 management is growing, antiviral medication is still the first line of treatment. Therefore, it is critical that effective, safe, and tolerable antivirals be available to treat early COVID-19 and stop its progression.
View Article and Find Full Text PDFJ Cell Physiol
January 2025
Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
Vascular regeneration plays a vital role in tissue repair yet is drastically impaired in those with a spinal cord injury (SCI). Pericytes are of great significance as they are entwined with vessel-specific endothelial cells and actively contribute to maintaining the spinal cord's vascular network. Within the neurovascular unit (NVU), subtypes of pericytes characterized by various markers such as PDGFR-β, Desmin, CD146, and NG-2 are involved in vascular regeneration in SCI repair.
View Article and Find Full Text PDFDiabetol Metab Syndr
January 2025
Laboratory of Immunopharmacology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation-Fiocruz, Campus Maré. Centro de Pesquisa, Inovação e Vigilância em Covid-19 e Emergências Sanitárias. Endereço: Av. Brasil, 4036-Bloco 2. Manguinhos, Rio de Janeiro, RJ, CEP 21040-361, Brazil.
Introduction: Metabolic syndrome (MetS) is a metabolic disorder related to obesity and insulin resistance and is the primary determinant of the development of low-intensity chronic inflammation. This continuous inflammatory response culminates in neuroimmune-endocrine dysregulation responsible for the metabolic abnormalities and morbidities observed in individuals with MetS. Events such as the accumulation of visceral adipose tissue, increased plasma concentrations of free fatty acids, tissue hypoxia, and sympathetic hyperactivity in individuals with MetS may contribute to the activation of the innate immune response, which compromises cerebral microcirculation and the neurovascular unit, leading to the onset or progression of neurodegenerative diseases.
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