CNS & Neurological Disorders - Drug Targets (Formerly Current Drug Targets - CNS & Neurological Disorders) - Volume 10, Issue 1, 2011

Parkinson's Disease: Kinase Busters to the Rescue? Parkinson's disease (PD) was first described in the essay entitled “An Essay of the Shaking Palsy” by James Parkinson in 1817. PD is the most common neurodegenerative movement disorder, whose neuropathological hallmarks are characterized by progressive and profound loss of neuromelanin-containing dopaminergic neurons in the substantia nigra pars compacta with the pres Read More

Inflammatory processes in the central nervous system (CNS) are of acute relevance to the pathogenesis and progression of several important neurological disorders. While multiple sclerosis (MS) is often quoted as one of the most striking examples of an inflammatory neurodegenerative condition, it is now widely recognized that inflammatory processes, particularly the innate immune responses, play a crucial role also in t Read More

Innate immune responses in the central nervous system must be tightly regulated as unrestrained activation generates a chronic inflammatory environment that can contribute to neurodegeneration and autoimmunity. Microglia express a wide variety of receptors of the innate immune system and are competent responders to danger. Toll-like receptor-, NOD-like receptor- and RIG1-like receptor mediated activation of mi Read More

Innate immunity is an arsenal of molecules and receptors expressed by professional phagocytes, glial cells and neurons and involved in host defence and clearance of toxic and dangerous cell debris. However, any uncontrolled innate immune responses within the central nervous system (CNS) are widely recognized as playing a major role in the development of autoimmune disorders and neurodegeneration, with multiple Read More

Under pathological conditions microglia (resident CNS immune cells) become activated, and produce reactive oxygen and nitrogen species and pro-inflammatory cytokines: molecules that can contribute to axon demyelination and neuron death. Because some microglia functions can exacerbate CNS disorders, including stroke, traumatic brain injury, progressive neurodegenerative disorders such as Alzheimer's disease, Parkinson' Read More

Epidemiological studies suggest that systemic use of non-steroidal anti-inflammatory drugs (NSAIDs) can prevent or retard the development of Alzheimer's disease (AD). However, clinical trials investigating the effects of NSAIDs on AD progression have yielded mixed or inconclusive results. The aim of this review is to distinguish the role of inflammation and the molecular targets of NSAIDs in the different stages of AD pathol Read More

For the development of novel central nervous system (CNS) drugs to promote neuroprotection, it is helpful to gain a better understanding of natural neuroprotective phenomena. Microglia play key roles in endogenous neuroprotective pathways and their activation is a common theme in several neurodegenerative disorders. Yet, while it is widely appreciated that activated microglia can have neuroprotective qualities, their contrib Read More

The nervous system is a unique network of different cell types and comprises a variety of proteins, lipids, and carbohydrates that have an important interplay with all major organs in the body. Homeostatic regulation of nervous tissue turnover must be carefully controlled, taking into account interactions of the nervous, endocrine, and immune systems. Clinical conditions affecting the nervous system range from mild c Read More

Microglia, the tissue macrophages of the brain, have under healthy conditions a resting phenotype that is characterized by a ramified morphology. With their fine processes microglia are continuously scanning their environment. Upon any homeostatic disturbance microglia rapidly change their phenotype and contribute to processes including inflammation, tissue remodeling, and neurogenesis. In this review, we will address func Read More

Major Depressive Disorder (MDD) is an extremely disabling, chronic and recurrent disease. Moreover, subthreshold depressive symptoms often persist during periods of apparent remission. Such symptoms include sleep disturbances, sexual dysfunction, weight gain, fatigue, disinterest, anxiety, and/or emotional blunting, which do not often respond to available antidepressant treatments. Agomelatine is a melatonergic a Read More

The treatment of Alzheimer's disease is undoubtedly one of the greatest challenges of modern medicine and pharmacology. Affecting millions of people, Alzheimer's disease has become a major social problem. Several theories have been proposed to account for its pathogenesis. Possibly, the “amyloid cascade hypothesis” is the dominant one. However, the “inflammation hypothesis” also contributes to the pathogenesis of the Read More

Neisseria meningitidis (N. meningitidis) causes sepsis, epidemic meningitis, and sometimes also meningoencephalitis. Despite early antibiotic treatment, mortality and morbidity remain significant. We present recent studies on meningococcal disease with focus on the pathophysiology caused by bacterial virulence factors and the host immune responses. The bacterial outer membrane lipopolysaccharide and non-lipopo Read More