The need
N 85 persons (or 106 million people) will suffer from AD [1]. The need to counter these disorders, based on improved mechanistic understanding of their etiopathogenesis cannot, therefore, be underestimated. The main pathological features of AD are the extracellular deposition of amyloid peptide (A) into plaques and the formation of intracellular tangles composed of hyperphosphorylated Tau protein [2]. Various lifetime parameters, such as chronic stress and exposure to* Correspondence: japalha@ecsaude.uminho.pt 1 Life and Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Campus Gualtar, Braga 4710-057, Portugal 2 ICVS/3B’s – PT Government Associate Laboratory, Braga/Guimaraes, Portugalinflammatory stimuli have been suggested to predispose individuals to AD, and several molecular pathways have been implied in the disease [3,4]. In this review we will focus on the involvement of the brain barriers in aging and in AD. This topic is still poorly investigated, especially in normal aging, but is of relevance given the ability of the brain barriers to maintain and regulate the environment for the normal neuronal activity. Thus, alterations in the barriers’ morphology, secretome and functioning can compromise central nervous system (CNS) homeostasis. A key message from this review is that the brain barriers are not mere obstacles to the passage of molecules, cells and drugs into and 3-Bromo-4-(propan-2-yloxy)aniline hydrochloride out of PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/13485127 the brain (which by itself is of relevance for 2-Bromo-4-fluoro-5-methylbenzoic acid clearance of A peptides); in fact, they actively contribute to brain homeostasis and display specific responses to events that occur in the periphery and in the brain parenchyma, which should be taken into consideration in understanding diseases of the CNS.The barriers of the brainCNS homeostasis is essential for the proper functioning of brain cells. The blood rain barriers participate in CNS?2013 Marques et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Marques et al. Molecular Neurodegeneration 2013, 8:38 http://www.molecularneurodegeneration.com/content/8/1/Page 2 ofhomeostasis by preventing the brain from being exposed to the constant oscillations in the concentration of blood constituents and by transporting nutrients and products from brain metabolism in and out of the brain, respectively. Two main barriers separate the CNS from the periphery: the blood rain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB) [5]. While the BBB has been well recognized for long; the BCSFB is more rarely mentioned, which is to regret when considering its functions, which include producing most of the cerebrospinal fluid (CSF). The existence of the brain barriers is in part responsible for the initial concept that the brain is an immuneprivileged site, with restricted passage of immune cells into PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/8086425 the brain. In fact, even though in a healthy person under physiological conditions, immune cell migration across the brain barriers is low, some migration exists and is required for the immune surveillance of the CNS [6,7]. However, during normal aging and in several diseases of the CNS, such as multiple sclerosis and AD, changes in blood composition, brain inflammation and the facilitated entrance of immune cells through the.