Current Topics in Medicinal Chemistry - Volume 9, Issue 10, 2009

Full text available

Parkinson's disease (PD) is characterized by the selective loss of dopamine (DA) neurons in the substantia nigra compacta (SNc). The transcription factor Pitx3 is important for the differentiation and maintenance of midbrain DA neurons during development. There is highly restricted and constitutive expression of Pitx3 in the SNc and ventral tegmental area (VTA) of the midbrain after birth. In addition to its importance duri Read More

Parkinson's disease (PD) is a complex neurodegenerative disorder characterised by dopaminergic cell loss in the substantia nigra. In addition, neurodegeneration occurs at a number of extra-nigral locations and involves a variety of non-dopaminergic neurotransmitter systems. Etiopathogenic mechanisms leading to cell death include oxidative stress and free radical generation, mitochondrial dysfunction, glutam Read More

Autophagy is the mechanism through which cells degrade oxidized membranes-organelles and mis/unfolded proteins, in this latter function cooperating with the ubiquitin-proteasome system (UP system). Although autophagy has been known for a long time, its involvement in the pathogenesis of neurodegenerative diseases has been investigated only recently. The most fascinating data are very recent and show a Read More

L-DOPA is a di-hydroxy-phenyl, catecholamine precursor, amino acid, initially considered as an inert compound and now the key stone for the treatment of Parkinson's disease (PD) and some hereditary dystonias. L-DOPA, when administered to mammals, is rapidly metabolized to dopamine and 3-OM-DOPA, and its half-life in plasma is roughly 2 hours which has been considered the explanation for some of the L-DOPA related Read More

The intermittent oral intake of the dopamine (DA) precursor L-3,4-dihydroxyphenylalanine (L-DOPA) is the classic therapy of Parkinson's disease (PD). In this way, the drug precursor can be metabolised into the active neurotransmitter DA. Although this occurs throughout the brain, the therapeutic relief is believed to be due to restoring extracellular DA levels within the dorsal striatum (more in the putamen than the cau Read More

Parkinson disease (PD) is an already prevalent neurodegenerative disease that is poised to at least double over the next 25 years. Although best known for its characteristic movement disorder, PD is now appreciated commonly to cause cognitive impairment, including dementia, and behavioral changes. Dementia in patients with PD is consequential and has been associated with reduced quality of life, shortened surviv Read More

Idiopathic Parkinson's Disease (PD) is a progressive neurodegenerative disease characterized by dopaminergic neuronal loss within the substantia nigra. The degeneration of dopamine and other neuronal populations in PD lead to both chronic motor and non-motor disabilities but the mechanisms remain unclear. Molecular genetic studies in familial forms of the disease identified key proteins involved in PD pathogenesi Read More

This article describes recent advances in the development and biological evaluation of small molecule mGluR4 positive allosteric modulators (PAMs), and, to a lesser extent, orthosteric agonists. Due to its expression in the basal ganglia, the Family 3 GPCR metabotropic glutamate receptor subtype 4 (mGluR4) has recently garnered a great deal of attention as a putative target for the treatment of Parkinson's disease and a v Read More