Blood brain barrier dysfunction in healthy aging and dementia: Why, how, what for?

IF 12.5 1区 医学 Q1 CELL BIOLOGY Ageing Research Reviews Pub Date : 2024-06-29 DOI:10.1016/j.arr.2024.102395
Susana Cunha , Joana Bicker , José Sereno , Amílcar Falcão , Ana Fortuna
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Abstract

The blood brain barrier (BBB) is an indispensable structure that maintains the central nervous system (CNS) microenvironment for a correct neuronal function. It is composed by highly specialized microvessels, surrounded by astrocytes, pericytes, neurons and microglia cells, which tightly control the influx and efflux of substances to the brain parenchyma. During aging, the BBB becomes impaired, and it may contribute to the development of neurodegenerative and neurological disorders including Alzheimer’s disease and other dementias. Restoring the BBB can be a strategy to prevent disease onset and development, reducing the symptoms of these conditions. This work critically reviews the major mechanisms underlying BBB breakdown in healthy and unhealthy aging, as well as biomarkers and methodologies that accurately assess its impairment. Complementarily, potential therapeutic targets are discussed as new strategies to restore the normal function of the BBB in aging.

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健康老龄化和痴呆症中的血脑屏障功能障碍:为什么、如何、为了什么?
血脑屏障(BBB)是维持中枢神经系统(CNS)微环境以确保神经元正常功能不可或缺的结构。它由高度特化的微血管组成,周围有星形胶质细胞、周细胞、神经元和小胶质细胞,它们严格控制着物质流入和流出脑实质。在衰老过程中,BBB 会受损,并可能导致神经退行性疾病和神经系统疾病的发生,包括阿尔茨海默病和其他痴呆症。恢复 BBB 可作为预防疾病发生和发展的一种策略,从而减轻这些疾病的症状。本研究对健康和不健康老龄化过程中导致生物BB破坏的主要机制,以及准确评估生物BB损伤的生物标志物和方法进行了深入探讨。此外,还讨论了潜在的治疗靶点,作为恢复衰老过程中 BBB 正常功能的新策略。
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来源期刊
Ageing Research Reviews
Ageing Research Reviews 医学-老年医学
CiteScore
19.80
自引率
2.30%
发文量
216
审稿时长
55 days
期刊介绍: With the rise in average human life expectancy, the impact of ageing and age-related diseases on our society has become increasingly significant. Ageing research is now a focal point for numerous laboratories, encompassing leaders in genetics, molecular and cellular biology, biochemistry, and behavior. Ageing Research Reviews (ARR) serves as a cornerstone in this field, addressing emerging trends. ARR aims to fill a substantial gap by providing critical reviews and viewpoints on evolving discoveries concerning the mechanisms of ageing and age-related diseases. The rapid progress in understanding the mechanisms controlling cellular proliferation, differentiation, and survival is unveiling new insights into the regulation of ageing. From telomerase to stem cells, and from energy to oxyradical metabolism, we are witnessing an exciting era in the multidisciplinary field of ageing research. The journal explores the cellular and molecular foundations of interventions that extend lifespan, such as caloric restriction. It identifies the underpinnings of manipulations that extend lifespan, shedding light on novel approaches for preventing age-related diseases. ARR publishes articles on focused topics selected from the expansive field of ageing research, with a particular emphasis on the cellular and molecular mechanisms of the aging process. This includes age-related diseases like cancer, cardiovascular disease, diabetes, and neurodegenerative disorders. The journal also covers applications of basic ageing research to lifespan extension and disease prevention, offering a comprehensive platform for advancing our understanding of this critical field.
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