The blood-brain barrier as a treatment target for neurodegenerative disorders.

Ruslan Rust, Abhay P Sagare, Mingzi Zhang, Berislav V Zlokovic, Kassandra Kisler
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Abstract

Introduction: The blood-brain barrier (BBB) is a vascular endothelial membrane which restricts entry of toxins, cells, and microorganisms into the brain. At the same time, the BBB supplies the brain with nutrients, key substrates for DNA and RNA synthesis, and regulatory molecules, and removes metabolic waste products from brain to blood. BBB breakdown and/or dysfunction have been shown in neurogenerative disorders including Alzheimer's disease (AD). Current data suggests that these BBB changes may initiate and/or contribute to neuronal, synaptic, and cognitive dysfunction, and possibly other aspects of neurodegenerative processes.

Areas covered: We first briefly review recent studies uncovering molecular composition of brain microvasculature and examine the BBB as a possible therapeutic target in neurodegenerative disorders with a focus on AD. Current strategies aimed at protecting and/or restoring altered BBB functions are considered. The relevance of BBB-directed approaches to improve neuronal and synaptic function, and to slow progression of neurodegenerative processes are also discussed. Lastly, we review recent advancements in drug delivery across the BBB.

Expert opinion: BBB breakdown and/or dysfunction can significantly affect neuronal and synaptic function and neurodegenerative processes. More attention should focus on therapeutics to preserve or restore BBB functions when considering treatments of neurodegenerative diseases and AD.

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