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Regulation of haeme oxygenase-1 for treatment of neuroinflammation and brain disorders.

ABSTRACT: Injury to the CNS elicits a host defense reaction that utilizes astrocytes, microglia, neurons and oligodendrocytes. Neuroinflammation is a major host defense mechanism designed to restore normal structure and function after CNS insult, but like other forms of inflammation, chronic neuroinflammation may contribute to pathogenesis. The inducible haeme oxygenase isoform, haeme oxygenase-1 (HO-1), is a phase 2 enzyme upregulated in response to electrophilic xenobiotics, oxidative stress, cellular injury and disease. There is emerging evidence that HO-1 expression helps mediate the resolution of inflammation, including neuroinflammation. Whether this is solely because of the catabolism of haeme or includes additional mechanisms is unclear. This review provides a brief background on the molecular biology and biochemistry of haeme oxygenases and the actions of haeme, bilirubin, iron and carbon monoxide in the CNS. It then presents our current state of knowledge regarding HO-1 expression in the CNS, regulation of HO-1 induction in neural cells and discusses the prospect of pharmacological manipulation of HO-1 as therapy for CNS disorders. Because of recognized species and cellular differences in HO-1 regulation, a major objective of this review is to draw attention to areas where gaps exist in the experimental record regarding regulation of HO-1 in neural cells. The results indicate the HO-1 system to be an important therapeutic target in CNS disorders, but our understanding of HO-1 expression in human neural cells is severely lacking.

SUBMITTER: Syapin PJ

PROVIDER: S-EPMC2584924 | biostudies-other | 2008 Nov

REPOSITORIES: biostudies-other

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Project description:Resveratrol (RES) is a natural polyphenolic non-flavonoid compound present in grapes, mulberries, peanuts, rhubarb and in several other plants. Numerous health effects have been related with its intake, such as anti-carcinogenic, anti-inflammatory and brain protective effects. The neuroprotective effects of RES in neurological diseases, such as Alzheimer's (AD) and Parkinson's (PD) diseases, are related to the protection of neurons against oxidative damage and toxicity, and to the prevention of apoptotic neuronal death. In brain cancer, RES induces cell apoptotic death and inhibits angiogenesis and tumor invasion. Despite its great potential as therapeutic agent for the treatment of several diseases, RES exhibits some limitations. It has poor water solubility and it is chemically instable, being degraded by isomerization once exposed to high temperatures, pH changes, UV light, or certain types of enzymes. Thus, RES has low bioavailability, limiting its biological and pharmacological benefits. To overcome these limitations, RES can be delivered by nanocarriers. This field of nanomedicine studies how the drug administration, pharmacokinetics, and pharmacodynamics are affected by the use of nanosized materials. The role of nanotechnology, in the prevention and treatment of neurological diseases, arises from the necessity to mask the physicochemical properties of therapeutic drugs to prolong the half-life and to be able to cross the blood-brain barrier (BBB). This can be achieved by encapsulating the drug in a nanoparticle (NP), which can be made of different kinds of materials. An increasing trend to encapsulate and direct RES to the brain has been observed. RES has been encapsulated in many different types of nanosystems, as liposomes, lipid and polymeric NPs. Furthermore, some of these nanocarriers have been modified with targeting molecules able to recognize the brain areas. Then, this article aims to overview the RES benefits and limitations in the treatment of neurological diseases, as the different nanotechnology strategies to overcome these limitations.

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Regulation of haeme oxygenase-1 for treatment of neuroinflammation and brain disorders.

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