Free Content Editorial [Hot topic: Role of Inflammation in Neurological and Psychiatric Disorders (Guest Editor: Mohtashem Samsam)]

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Abstract:

Neuroinflammation is believed to be the common pathological process in many neurodegenerative diseases, and what was believed to be a naive housekeeping process, as a result of neurodegeneration, can be a hostile contributor of the disease. Several primary neurological disorders are associated with inflammatory responses, in many cases they aggravate the initial problem and lead to acute symptoms and disability or permanent damage due to neuronal death. Most of the anti-inflammatory treatment strategies in neurological disorders aim to reduce the symptoms of the disease leading to a rapid recovery in many cases due to blocking the immune response by inhibiting the pro-inflammatory mediators. There are evidences that inflammatory mediators including free radicals such as nitric oxide (NO) and reactive oxygen species (ROS), can contribute to neurodegenerative diseases in part by triggering protein misfolding [1]. Moreover, elevation of soluble tumor necrosis factor (TNF), a potent pro-inflammatory/ pro-apoptotic cytokine is one of the hallmarks of acute and chronic neuroinflammation as well as a number of neurodegenerative conditions including Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and demyelinating disease such as multiple sclerosis (MS), as well as the ischemic stroke [2, 3].

Multiple sclerosis (MS) is the most common inflammatory demyelinating disease of the central nervous system (CNS) characterized by inflammation, demyelination and variable loss of axons [4-6]. The recurrent relapses of CNS inflammation in MS patients cause disability. The Th17 cell response has been indicated in experimental allergic encephalomyelitis (EAE, a model to study MS) [7]. Treatment strategies include the acute treatment of relapses, symptomatic relief, and immunomodulation by constraining the inflammation, stimulation of remyelination and neuroprotection. Relapses have long been treated with anti-inflammatory drugs including the steroids [8]. Interferon beta (IFNβ)-1b was the first immunomodulatory drug used for MS [9]. Several other anti-inflammatory or immunomodulatory drugs are currently used in the treatment of MS [10]. A new treatment approach to reduce or prevent the ROS by Dr. Michel Geffard in France and Dr. Rafael Covenas in Spain and colleagues suggests using fatty acids linked to poly-L-Lysine (PL), such as antioxidants linked to PL, free radical scavengers linked to PL, and amino acids linked to PL inhibits brain leukocyte infiltration in EAE, the animal model of MS, and abolishes the episodes of the disease and preserves myelin integrity [11, 12].

In this issue, the article: endotherapia, will discuss how fatty acids, anti-oxidants, amino acids and their derivatives linked to the polymer poly-L-lysine have a better efficiency as anti-inflammatory drugs, an approach that prevents metabolic degradation of the linked small molecules, improves the kinetics and increases the half-life of the product, as well as allowing it to reach the site of the lesion. The result of an open study in treatment of MS patient is presented using this new approach.

Alzheimer's disease (AD) is a neurodegenerative disorder of the CNS associated with progressive cognitive and memory loss, and is characterized by senile plaques and deposition of amyloid beta peptide (Abeta), neurofibrilary tangles in brain tissue, degeneration of cholinergic pathways, and neuronal degeneration in brain including the cerebral cortex and the hippocampus [13]. Amyloid-beta and tau protein make up the plaques and tangles of Alzheimer's disease, where these normally soluble proteins assemble into amyloid-like filaments [14]. Inflammation also plays a role in AD and there are evidences for the convergence of the mechanisms responsible for the sensing, transduction, and amplification of inflammatory processes that result in the production of neurotoxic mediators [15, 16]. Gliosis which is known to be induced by oxidative stress and is increased by aging, significantly contributes to the pathophysiology of AD. Several other factors including the genetic, biological and environmental factors play important role in the pathogenesis of AD. Most genes conferring susceptibility to AD are related to amyloid- beta deposition (APP; PS1; PS2; APOE; Cystatin-C; ubiquilin-1), oxidative stress (NOS2; NOS3) as well as the inflammatory response (IL-1 alpha; IL-1 beta; IL-6; TNF-alpha) genes [17-21]. Amyloid-beta oligomers and fibrils and their cellular effects can activate the innate immunity defense and induce inflammatory and apoptotic responses in human brain. Several antiinflammatory drugs approved for other conditions, when used in AD counteract the inflammatory responses [22]. The cyclooxygenase (COX) inhibitors, such as aspirin and indomethacin, have been tested as potential therapeutics in AD [23, 24], but due to their side effects on stomach by interfering with production of eicosanoids such as prostaglandin (PGs, which have gastroprotective effects), as well as mediating to bronchoconstriction through other eicosanoids including the leukotriense (LTs), the COX-2 inhibitor drugs were proposed. However, the COX-2 inhibitors, which may reduce the production of prostaglandins, may increase the production of LTB4 which is one of the most potent endogenous chemotactic/inflammatory factors....

Document Type: Research Article

Publication date: September 1, 2010

More about this publication?
  • Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry aims to cover all the latest and outstanding developments in medicinal chemistry and rational drug design for the discovery of new Anti-Inflammatory & Anti-Allergy Agents.

    Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of current topics in Anti-Inflammatory & Anti-Allergy Medicinal Chemistry.

    Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments in Anti-Inflammatory & Anti-Allergy Agents drug discovery.
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