CNS & Neurological Disorders - Drug Targets (Formerly Current Drug Targets - CNS & Neurological Disorders) - Volume 11, Issue 4, 2012

The Society for the Study of Neuroprotection and Neuroplasticity (SSNN) was created in 2005 by an international group of clinicians and basic scientists under the initiative of Prof. Dafin F. Muresanu, University of Medicine and Pharmacy “Iuliu Hatieganu”, Cluj-Napoca, Romania. The SSNN is a scientific organization focusing on basic and clinical research, whose goal is to create a discussion platform to facilitate our understan Read More

Pain is a fundamental experience characterized by an unpleasant physical perception and corresponding emotional state. Disease or trauma affecting the peripheral or central neuronal sensory pathway can produce a form of chronic pain known as neuropathic pain. This pain may occur with central nervous system disorders, such as stroke or multiple sclerosis, or with conditions associated with peripheral nerve damage, Read More

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Cell replacement therapies are an attractive mode of treatment for neurodegenerative disorders as they have the potential to alleviate or modify disease symptoms and restore function. In Parkinson's disease, the cell type requiring replacement is dopamine-producing neurons of the midbrain. The source of replacement cells is contentious, with opinion still evolving. Clinical trials have previously used fetal brain tissue; however, Read More

Tyrosine hydroxylase (TH) is the rate-limiting enzyme in brain catecholamine biosynthesis, and tetrahydrobiopterin is its cofactor. Research has focused on identifying mechanisms of TH activity regulation. TH activity is modulated by the cofactor itself, and is enhanced by several kinases phosphorylating key serines in the TH regulatory domain. Aside from these, the mechanisms that control TH gene transcription and TH Read More

The nigrostriatal pathway is very likely involved in sleep regulation, considering the occurrence and high prevalence of sleep-related disorders in patients with Parkinson's disease. Indeed, dopaminergic neurons in the ventral tegmental area were recently shown to fire in bursts during paradoxical sleep (PS), but little is known about the activity of the nigrostriatal dopamine (DA) cells in relation to PS. In view of that we h Read More

Parkinson's disease (PD) is characterized by the progressive loss of the dopaminergic neurons leading to decrease in striatal dopamine (DA) levels. In the present review, our focus was on recent advances in the treatment procedures of PD to achieve an increase in deficient tyrosine hydroxylase (TH) activity and/or expression. Stimulation of residual TH activity by the cofactors, 6R-L-erythro-tetrahydrobiopterin (BPH4) or NADH, or Read More

Tyrosine hydroxylase (TH) is the rate limiting step in the biosynthesis of dopamine and other catecholamines. Differences have been noted in concentration and availability of this enzyme and its cofactors in disease states such as Parkinson's disease (PD) which are subject to alterations in catecholamines. More evidence suggests in fact that TH may play a direct role in the pathogenesis of PD, especially through oxidative st Read More

Neurodegenerative Parkinson's disease (PD) is a multifactorial disorder; effects like alpha synuclein aggregation, low dopamine levels and dopaminergic neurodegeneration are considered to be hallmarks of the disease. Several recent studies have pointed towards an important role of enzyme tyrosine hydroxylase (TH) in the pathophysiology of PD. We embarked on the present studies to explore the mechanistic role of Read More

Parkinson's disease (PD) is a common chronic progressive neurodegenerative disorder in elderly people. A consistent neurochemical abnormality in PD is degeneration of dopaminergic neurons in substantia nigra pars compacta, leading to a reduction of striatal dopamine (DA) levels. As tyrosine hydroxylase (TH) catalyses the formation of Ldihydroxyphenylalanine (L-DOPA), the rate-limiting step in the biosynthesis of DA, the disea Read More

Although researchers are pursuing “disease modifying” medications to slow or stop Parkinson's disease (PD) progression, a myriad of agents with protective properties in cell cultures and animal models have yielded few treatments in clinical practice. Developing safe and effective treatments with disease-modifying/neuroprotective mechanisms of action and identifying patients in the pre-motor phase will be a challenge. The i Read More

Oxidant molecules generated during neuronal metabolism appear to play a significant role in the processes of aging and neurodegeneration. Increasing experimental evidence suggests the noteworthy relevance of the intracellular reduction-oxidation (redox) balance for the dopaminergic (DA-ergic) neurons of the substantia nigra pars compacta. These cells possess a distinct physiology intrinsically associated with elevated Read More

Parkinson's disease (PD) is related to excess production of reactive oxygen species (ROS) or inadequate and impaired detoxification by endogenous antioxidants, alterations in catecholamine metabolism, alterations in mitochondrial electron transfer function, and enhanced iron deposition in the substantia nigra. The concept that oxidative stress is an important mechanism underlying the degeneration of dopaminergic (DAergic) n Read More

Classically, Parkinson's disease (PD) is considered to be a motor system affliction and its diagnosis is based on the presence of a set of cardinal motor signs (e.g. rigidity, bradykinesia, rest tremor and postural reflex disturbance). However, there is considerable evidence showing that non-motor alterations (e.g. anxiety, depression, sleep, gastrointestinal and cognitive functions) precede the classical motor symptoms seen i Read More

Tyrosine hydroxylase (TH) is the rate limiting enzyme responsible for converting tyrosine to L-DOPA in the dopamine synthesis pathway. The pathophysiology of Parkinson's disease (PD) is largely due to the nigrostriatal dopaminergic system, with a decrease in TH activity, TH synthesis and TH mRNA in the striatum of PD and animal experimental models. TH is thus one of the main targets for gene therapy in PD. TH activity v Read More

Parkinson's disease (PD) is associated with neurodegeneration of the nigrostriatal tract and is accompanied with loss of tyrosine hydroxylase (TH) and dopamine (DA). Development of neuroprotective strategies targeting PD is often undermined by lack of proper understanding of processes contributing to the pathology. In this mini review we have tried to briefly outline the involvement of TH and α-synuclein in PD. Aberrant e Read More

Parkinson's disease is a major age-related neurodegenerative disorder. As the classical disease-related motor symptoms are associated with the loss of dopamine-generating cells within the substantia nigra, tyrosine hydroxylase (TH), the rate-limiting enzyme in the synthesis of catecholamines has become an important target in the development of Parkinson's disease drug candidates, with the focus to augment Read More

The tyrosine hydroxylase (TH) gene encodes a monoxygenase that catalyzes the rate limiting step in dopamine biosynthesis. A hallmark of Parkinson's disease (PD) is the loss of dopaminergic neurons in the substantia nigra. Consistent with the essential role of TH in dopamine homeostasis, missense mutations in both alleles of TH have been associated with severe Parkinsonism-related phenotypes including infa Read More

Alzheimer's disease (AD) and type 2 diabetes mellitus (T2DM) are two debilitating health disorders afflicting millions worldwide. Recent research has revealed similarities between AD and T2DM. Both these protein conformational disorders are associated with obesity, insulin resistance, inflammation and endoplasmic reticulum stress, en-route initiation and/or stage aggravation. In this mini review we have tried to summ Read More