Neuroprotection and neurodegenerative diseases: from biology to clinical practice.
Neurodegenerative diseases and, in particular, Alzheimer disease, are characterized by progressive neuronal loss correlated in time with the symptoms of the disease considered. Whereas the symptoms of those incapacitating diseases are beginning to be managed with a relative efficacy, the ultimate objective of therapy nonetheless remains preventing cell (neuronal and/or astrocytic) death in a neurocytoprotective approach. In biologic terms, in the light of progress at basic research level, three strategies may be envisaged: (1) antagonizing the cytotoxic causal events (excess intracellular calcium, accumulation of abnormal proteins, excitotoxic effects of amino acids, oxidative stress, processes related to inflammation, etc.); (2) stimulating the endogenous protective processes (anti-free radical or DNA repair systems, production of neurotrophic factors, potential cytoprotective action of steroids, etc.); (3) promoting damaged structure repair strategies (grafts) or deep brain or cortical neurostimulation with a view to triggering (beyond the symptomatic actions) potential 'protective' cell mechanisms. The clinical transition of the various strategies whose efficacy is being tested in animal and/or cell models, experimental analogs of the diseases, and thus the objective demonstration in humans of pharmacological and/or surgical neurocytoprotection, is currently the subject of considerable methodological debate (What are the right psychometric assessment criteria? What are the most pertinent laboratory or neuroradiological markers, etc.?). A number of clinical trials have been completed or are ongoing with drugs that are reputed to be neuroprotective. Thus, elements of the response are beginning to be generated with a view to determining whether it will soon be possible to effectively slow or even stop the neurodegenerative process whose etiology, in most cases, remains obscure.
Akwa
Yvette
Y
INSERM U488, Le Kremlin-Bicêtre, France.
Allain
Hervé
H
Bentue-Ferrer
Danièle
D
Berr
Claudine
C
Bordet
Régis
R
Geerts
Hugo
H
Nieoullon
André
A
Onteniente
Brigitte
B
Vercelletto
Martine
M
D000544:Alzheimer Disease / Q000503:physiopathology* / Q000517:prevention & control; D017209:Apoptosis / Q000187:drug effects*; D002986:Clinical Trials as Topic; D006801:Humans; D019636:Neurodegenerative Diseases / Q000503:physiopathology* / Q000517:prevention & control; D009474:Neurons / Q000502:physiology*; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use
D018696:Neuroprotective Agents