Forexample, MK I has been found to prevent completely striatal dopam ine depletion at earlytime points after adm in is tration ofMPTP to mice, whereas no protective effect was observed atlater times. Ano therfactor thatmay con tr ibu te to the actionofNMDA antagonists as well as to the conflicting da ta on the ir effects on MPTP neurotoxicity is the fact that MK I has been reported to modify the rateof eliminationof MPP from the mouse striatum. These conc lusionsare comp atible with findingsof studies on P a rk in son sdisease,prov id ing ev idence in favorof the occurrenceof ox idative stress,mi to chondri alabno rm ali ties, and excito tox icity. Whiledata conce rn ing a possible failure inmi to chondrialresp ira tory ch a in activity in the skeletal muscle rem a in con trovers ial sults have been ob ta ined by comp aring spec imensfrom the substantia nigraof patien ts vs controlsubjects. Indeed, abno rmalitiesin the nigral tissue appearto be ra therselective formi tochondrial comp lex I.Itis also no teworthy th at theroleof EAA recep tors may vary depend ing upon recep, suggesting th atnigrostriatal damage may be theresultof mo lecu larchanges more comp lex a nd selective th an previously thoughtand emphasiz ing theneed for mo re de tailed pha rmaco log ic and toxicologic studies.Such selectiv ity may be furtherenh ancedifEAA induced celldam ageis associated withother neu ro tox icme ch anismswhichmay themse lves target specific popu lationsofneu rons. O ther critical featuresof neu rodegene rativedisorders are theirde layed onsetand gradually progressive evo lution. Bothof these charac ter istics may result from thed evelopm entof me tabolic abno rmalitieswhich mayrenderneu ronspro gressively mo re susceptible to excitotoxicity. Thus, excitotoxicity cou ld exp la in a numberof featuresof neu rodegene rative disorders, lead ing to the hypo thes is th atit may representthe final common pa thwayof neu ronaldea th. This hypo thes is also po ints to alte rations in energy me tab olism as the most likely mechanism which wou ld enh ance the susceptibility to EAA toxicity as well as the selectivity ofneu ron aldamage. SUMMARY A centralth emeth atemerges from this review is th atex ergetics andmi tochondrialfunction. Ox id ativestress and reduced intracellu larenergy levelscan in te ractto increaseboth ex a ted excito tox icity. Agerelatedor genetic alter ationsin an tiox id antdefenseme ch anismsand ormito chondri al functionmayrender ind iv iduals susceptib le to a varietyof environm entalneu ro tox ins.Threema jorpo ints clearly eme rge from thein teg ration of thevarious perspectivespre sen ted here: first, theva lueof Targetmol’s YK11 usingneu ro toxic ants as models foreluc idating thepa tho rological diseases: second, the high degreeof overlap th at exists be tweenproox id antand excita to ry events: and last, thefact that, whilemanyd iverse agen ts anddiseasescan cause selectivedam ageto thenervoussys tem, these specific pa tho log iesmay be underla id by a few ub iquitousvu lne ra ble features found in all neu raltissues.Excita to ry am ino ac ids acting as final commonm edia torsofneu ron aldea th appearto be oneofthose vu lne rab le features th atinteract with ho th pre and post synapticme ch anismsth ata re al te red hy theaging process.