Neurodegeneration diseases

Due to the numerous possible reactions and related biological consequences, inappropriate overproduction of NO can cause a series of disease states such as a variety of neurodegeneration diseases including inflammation, rheumatic disease, septic shock, diabetes melhtus, and cerebral ischemia. Therefore development of isoform-specific NOS inhibitors to regulate NO synthesis has been an active research area. 

Antagonists of metabotropic glutamate receptors and G-protein-coupled receptors associated with various neurodegenerate diseases have been prepared by proline-catalyzed direct a-amination reactions (Scheme 2.30) [7c]. Both, indane carbaldehyde 10 and analogous compounds having an ester functionality [leading to l-aminoindan-l,5-dicarboxylic acid (AIDA)] and or a phosphonate substituent [(RS)-l-amino-5-phosphonoindan-l-carboxylic acid APICA], all reacted with di-... 

Thiamine deficiency provides an important platform for modelling the pathophysiology of neurodegeneration disease. 

Adult dopamin-containing neurons in the substantia nigra rely on Cavl. 3 channels as pacemaker channels. It appears that the resulting enhanced Ca2+ load renders these channels more susceptible to neurotoxic effects and neurodegeneration as observed in Parkinson s disease. Preclinical evidence suggests that block of these with dihydropyridines causes a switch to a Cavl.3-independent pacemaker and protects these neurons from neurotoxicity. 

There are multiple mechanisms known to underlie the neuronal cell damage associated with injury or disease that at least theoretically could be targeted for pharmaceutical intervention. Currently however, there is no clinically available therapeutic agent that can reliably protect the brain from progressive neurodegenerative processes for sustained periods. Due to the extensive amount of preclinical research that has been conducted in recent years, there is a basis for optimism, however, it appears likely that some of these approaches will result in clinically effective therapeutic modalities in the near future. A short overview of some of the investigational approaches to combat neurodegeneration appears below. 

In summary, the steadily increasing size of geriatric populations in developed countries and the resultant increases in age-related diseases of the brain have provided the impetus for intensive study of the processes underlying neurodegeneration. A better understanding of these processes will likely lead to better methods of treatment not only for progressive memory disorders such as Alzheimer disease, but also for motor disorders such as amyotrophic lateral sclerosis, and cerebrovascular disorders such as stroke. 

Moss ML, Jin SL, MiUa ME et al (1997) Cloning of a disintegrin metalloproteinase that processes precursor tumour-necrosis factor-alpha. Nature 385 733-736 Nixon RA, Cataldo AM (2006) Lysosomal system pathways genes to neurodegeneration in Alzheimer s disease. J Alzheimers Dis 9 277-289 Noorbakhsh F, VergnoUe N, HoUenberg MD et al (2003) Proteinase-activated receptors in the nervous system. Nat Rev Neurosci 4 981-990... 

Ben-Shackar, D., Eshel, G., Riederer, P. and Youdim, M.B.H. (1992). Role of iron and iron chelation in dopaminergic-induced neurodegeneration implications for Parkinson s disease. Ann. Neurol. 32, S105-S110. 

Neurodegeneration Localised or widespread death of neurons, a feature of a number of brain disorders, such as Alzheimer s disease, Parkinson s disease and cerebrovascular stroke. It can also be caused by neurotoxic drugs like MDMA/Ecstasy, although there is debate over whether this occurs in humans as well as laboratory animals. 

Nucleus basalis of Meynert One of the forebrain structures where neurodegeneration occurs in Alzheimer s disease. 

Parkinson s disease A basal ganglia disorder characterised by neurodegeneration of... 

Neurotrophic factors Mainly conditions caused by/associated with neurodegeneration, including peripheral neuropathies, amyotrophic lateral sclerosis and neurodegenerative diseases of the brain... 

PRNP mutations cause neurodegeneration and influence disease progression 662... 

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