CNS & Neurological Disorders - Drug Targets (Formerly Current Drug Targets - CNS & Neurological Disorders) - Volume 7, Issue 1, 2008

Neurons are typically post-mitotic cells. This means that they are expected to have a life span comparable to that of their carriers. Unfortunately, sometimes, they die prematurely as a result of complex processes known as “neurodegeneration”. Neurodegenerative diseases are now generally considered a group of disorders that seriously and progressively impair the functions of the nervous system through causing the selectiv Read More

Oxidative stress occurs early in the progression of Alzheimer disease, significantly before the development of the pathologic hallmarks, neurofibrillary tangles and senile plaques. All classes of macromolecules (sugar, lipids, proteins, and nucleic acids) are affected by oxidative stress leading, inevitably, to neuronal dysfunction. Extensive data from the literature support the notion that mitochondrial and metal abnorma Read More

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of motor neurons resulting in progressive paralysis and respiratory failure. About 1 in every 400 people dies of ALS, usually within 3 to 5 years of symptom onset. The lack of effective therapy means that although the incidence is comparable to that of multiple sclerosis, the prevalence is low. The causes of ALS are largely unknown, but the only disease- Read More

This review deals with the results showing the relation between vitamin B12 deficiency and neurotoxicity of homocysteine and nitrite (a metabolite of nitric oxide) in Parkinson's patients treated with levodopa (L-Dopa). We have already reported a linear relationship between the CSF levels of nitrite with glutamic acid and homocysteine suggesting that the production of nitrite is interrelated with the neurotoxic level of homocyst Read More

Parkinson's disease (PD) is the second leading age-related degenerative brain disease in the world affecting millions of people. This neurological disorder disrupts the quality of life of patients and their families, exerts an enormous emotional and physical strain on caregivers, and has a large cost for society. Moreover, the increasing numbers of elderly people in the population will result in a sharp increase in the prevalence of Read More

Neurotrophic factors were originally identified based on their ability to prevent naturally occurring cell death in the developing nervous system. Many of these proteins also promote survival after injury or protect neurons in toxin-disease models in animals. In addition to neuroprotective effects, these factors exert trophic effects on neurons, stimulating increases in neuronal metabolism, cell size, and process outgrowth. T Read More

The neurotrophins are a family of closely related proteins that were first identified as survival factors for sympathetic and sensory neurons, and have since been shown to control a number of aspects of survival, development and function of neurons in both the central and peripheral nervous systems. Limiting quantities of neurotrophins during development control the numbers of surviving neurons to ensure a match between Read More

Ligand-independent and/or proNGF-induced p75NTR signaling has emerged as a potential major contributor to a number of pathological states, including axotomy-induced death, motor neuron degeneration, neuronal degeneration in Alzheimer's disease and oligodendrocyte death following spinal cord injury. A long standing goal in the neurotrophin field has been the development of non-peptide, small molecules capable of fu Read More

Neurotrophic factors, and in particular the neurotrophins, restore the function of damaged neurons and prevent apoptosis in adults. The potential therapeutic property of the neurotrophins is however, complicated by the peptidergic structure of these trophic factors, which impairs their penetration into the brain parenchyma, and therefore makes their pharmaco-therapeutic properties difficult to evaluate. In this article w Read More

The signaling pathways which contribute to neuronal death during development, aging and disease have been extensively studied. While initial efforts focused on developmental death, increasing evidence suggests that mitogenactivated protein kinase pathways play a role in human pathology. In particular, the c-Jun N-terminal kinases (JNKs), mitogen- activated protein kinases activated by extracellular stimuli includin Read More

Embryonic stem cells (ESC) are a source of renewable cells, which possess a phenomenal potential to differentiate into a myriad of cell types. Thus, ESCs offer a potentially unlimited supply of cells, which can be deployed in developing cell-based therapies. The in vitro differentiation capacity of ESC into derivatives of the neuronal lineage has been demonstrated and the functionality of the ESC derived neuroprogenitors, upon tra Read More

Neurotrophic factors comprise a broad family of secreted proteins that have growth promoting, survival promoting and differentiation inducing activities. Disruption of neurotrophic factor signalling is a characteristic of many central and peripheral nervous system disorders, such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis, stroke, and peripheral neuropathy and pain. It Read More