Neurodegenerative disease chronic

In terms of clinical proof of neuroprotective effects in chronic neurodegenerative diseases, so far there are promising clinical results in ATS only with riluzole, and even then, the increase of survival obtained was only modest. The failure of r emacemide in a recent study in Huntington s disease was clearly a big setback. On the other hand, the moderate-affinity NMDA receptor antagonist memantine provides clear symptomatic improvement in dementia in both clinical and preclinical situations, and the precHnical data predict neuroprotective effects, substantiated by numerous animal models. 

AMPA receptor antagonists acting at the 2,3-benzodiazepine modulatory site seem to have a better safety profile than competitive agents such as NBQX, probably due to their better solubility and associated reduced side-effects such as renal toxicity. It is still not clear for which indications they might be useful, although their effects in animal models of acute and chronic neurodegenerative diseases look quite promising. 

Minghetti L., Ajmone-Cat M. A., De Berardinis M. A., and De Simone R. (2005). Microglial activation in chronic neurodegenerative diseases roles of apoptotic neurons and chronic stimulation. Brain Res. Rev. 48 251-256. 

Fiskum G., Murphy A. N., and Beal M. F. (1999). Mitochondria in neurodegeneration Acute ischemia and chronic neurodegenerative diseases. J. Cereb. Blood Flow Metab 19 351-369. 

It is of interest that idazoxan was tested in Parkinson s disease, although this indication was abandoned for lack of efficacy (F. Colpaert, personal communication). Efaroxan and its active dextro enantiomer dexefaroxan are also potent and selective centrally acting (X2 adrenoceptor antagonists (Bauer et al. 2003 Rizk et al. 2006). Efaroxan was developed for the treatment of chronic neurodegenerative diseases but abandoned because of side effects (P. Sokoloff, personal communication). 

Function of Norepinephrine in Neuroinflammation and Chronic Neurodegenerative Diseases... 

Pathological activation of glutamate receptors is a common feature and one of the primary causes of neuronal death in acute neuronal injury (such as trauma, epilepsy, and brain ischemia) and chronic neurodegenerative diseases (such as Parkinson s disease, Alzheimer diseases, amyotrophic lateral sclerosis, and AIDS dementia) (Choi, 1988 Doble, 1999 Lipton and Rosemberg, 1994). In particular, elevation of extracellular glutamate level is a key factor in the development of neuronal damage under ischemic conditions. 

Wada A, Yokoo H, Yanagita T, Kobayashi H. Lithium potential therapeutics against acute brain injuries and chronic neurodegenerative diseases. J Pharmacol Sci 2005 99(4) 307-21. 

Silva EA, Otsuki K, Leite AC, Alamy AH, Sa-Carvalho D, Vicente AC (2002) HTLV-n infection associated with a chronic neurodegenerative disease Clinical and molecular analysis. J Med Virol 66 253-257. 

NADPH oxidases (NOX), catalyzing the reduction of molecular oxygen to form the superoxide radical anion (02 ) and hydrogen peroxide (H202), are involved in stroke, diabetes, atherosclerosis, and chronic neurodegenerative diseases. GKT136901 is a novel NOX-1/4 inhibitor with potential application in the areas of... 

Glutamate is also involved in chronic neurodegenerative diseases such as Alzheimer, Parkinson, etc., but the most promising field in the chronic conditions is related to the pathogenesis of neuropathic pain and recent data support a key role for NMDA in this respect. 

Fiskum G, Murphy AN, Beal MF (1999) Mitochondria in neurodegeneration acute ischemia and chronic neurodegenerative diseases. J Cereb Blood Row Metab 19 351-369 Gallagher S (2004) Neurocognitive models of schizophrenia a neurophenomenological critique. Psychopathology 37 8-19... 

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