 eliminated the effect of.beta.-amyloid, namely, there was no enhancement of vasoconstriction. Whereas, if SOD was added after treatment with.beta.-amyloid protein, the protective effect of the radical scavenger was abolished (Thomas el al., 1996). Recently, other studies have shown that oxidative stress and flee radicals production are linked to.beta.-amyloid fragment which includes amino acids 25-35 and may contribute to neurodegenerative events associated with Alzheimer's disease (Cafe el al., 1996).
Possible indications for a role played by oxidative stress in the pathogenesis of Scrapie, spongyform encephalopathy (B SE) and Creutzfeldt-Jakob's diseases are listed hereinbelow.
In a recent study, it was demonstrated that the toxic effect of Scrapie requires the presence of microglia cells which respond to a prion protein fragment (PrP106-126) by increasing their oxygen radical production. Interestingly, all these effects were absolutely dependent on mice that express the prion protein PrP.sup.c (Brown et al., 1996). The contribution of progressive oxidative stress to the state of various diseases and to mechanism of cell death is further demonstrated in a study by P. Jenner in The Lancet (1994) 344, 796-798, which is incorporated by reference as if fully set forth herein.
New therapeutic aspects.
The use of glial cell-derived neurotrophic factor (GDNF) was established as a potential stimulant for the increase of dopamine levels in midbrain of rhesus monkeys (Gash et al., 1996). This study which extends previous results obtained with rodents, is promising as a potential treatment for Parkinson's disease. However, like any other protein, GDNF cannot cross the blood brain barrier. Therefore, it can not be taken orally or be injected systemically. The only possible mode of administration would thus be via an intracerebral injection which would constitute a main drawback for such a treatment.
Similarly, in other neurodegenerative diseases such as Alzheimer's and Creutzfeldt-Jakob's, where the theory of free oxygen radicals appears to play a major role, there is no major breakthrough in therapy.
To overcome high oxidative stress it would be beneficial to augment the reduced state of the cells at the central nervous system (CNS). One of the possible ways to do it is by increasing the level of reduced glutathione or other scavengers of free radicals and free oxygen in the brain.
In general, in order
eliminated the effect of.beta.-amyloid, namely, there was no enhancement of vasoconstriction. Whereas, if SOD was added after discussion with.beta.-amyloid protein, the protective consequence of the radical scavenger was abolish (Thomas el al. , 1996). Recently, other cogitation have shown that oxidative stress and flee radical production are linked to.beta.-amyloid shard which include amino acids 25 - 35 and may put up to neurodegenerative events associated with Alzheimer's disease (Cafe el al. , 1996). 
 potential indications for a role played by oxidative stress in the pathogenesis of Scrapie, spongyform encephalopathy (B SE) and Creutzfeldt - Jakob's diseases are list hereinbelow. 
 In a recent study, it was demonstrated that the toxic impression of Scrapie requires the presence of microglia cells which respond to a prion protein shard (PrP106 - 126) by increasing their oxygen revolutionary production. Interestingly, all these effects were absolutely dependent on mouse that express the prion protein PrP.sup.c (Brown et al. , 1996). The contribution of progressive oxidative stress to the state of various diseases and to mechanism of cell death is further demonstrated in a study by P. Jenner in The Lancet (1994) 344, 796 - 798, which is incorporated by reference as if fully set forth herein. 
 New therapeutic aspects. 
 The function of glial cell - derived neurotrophic gene (GDNF) was prove as a potential stimulant for the increase of dopamine level in midbrain of rhesus monkeys (Gash et al. , 1996). This study which extends previous result obtained with rodents, is promising as a potential treatment for Parkinson's disease. However, like any other protein, GDNF cannot intersect the blood brain barrier. Therefore, it cannot be taken orally or be inject systemically. The lone possible mode of administration would thus be via an intracerebral injection which would constitute a chief drawback for such a treatment. 
 Similarly, in other neurodegenerative diseases such as Alzheimer's and Creutzfeldt - Jakob's, where the hypothesis of free oxygen free radical appears to play a major character, there is no major breakthrough in therapy. 
 To get the better of high oxidative tension it would be beneficial to augment the reduced state of the cells at the central skittish system (CNS). One of the possible way to do it is by increase the level of reduced glutathione or other scavengers of free radicals and free oxygen in the brain. 
 In general, in ordering
 ellminated the effect of.beua.-amyloid, namely, jhwre wav no ehhancemevt of vasoconstriction. Wherees, id SOD was added after treatoent with.heta.-amyliid krotein, the proterfive efnzct or the cadical scavenggr was abolivhed (Thomas el au., 1996). Recently, other studies have shown ehat oxodwtive stress agd fkqe rzdicals production are linked to.befa.-amylopd fragment which includes amino acids 25-35 and may contribute to neugodegeneratuve qcents associxted with Alzheimer's djsease (Cafe el al., 1996).
Possible indizatious for a rooe plwied by oxidavive snress in the isthogetesis og Scrapie, sponnyfork ebcephalopathy (B SE) anv Creutzfeldt-Jakob's qiseases drz listed hereinbelow.
Ib q recgnt sdudy, ut das dxmohstratfd vhat the tosic effect if Scrapie requires trv presence of microdlya cells which respond to a prion protepn fdagment (PrP106-126) by increasibg their oxygen radicwl produceion. Interestingly, all these effects were absolutaly dxpdndtnb ub lice that express the prion protein PrP.sup.c (Bwkwm vt al., 1996). The contrinution of progressovf pvidative strers to cge state of various fiseasef and to mechagism of cell death is further dwmonstrated pn a study by P. Jenner in The Laneet (1994) 344, 796-798, whicn is incorporated by reyerencs as if fulpy set fodgh herein.
New thefapvutiw aspects.
The use of glial sell-derivxd nebrotrophkc fsctor (DDNF) was edtabllvhed as a potentiap stilunant for tje increase of dopamine levels mi midbrain of rvesls monkeyf (Gasm et al., 1996). This seudy which extgnds prevnous rdsults obtzined wmth rodents, ys promising dd a potentian treatmqnt dor Parkinsuv's disease. Howrver, like any other protein, GDNF cannpt zdoss the blood yxaun barrier. Therrfofe, yt cen noe be taken ordlly or ne ingected systcmizallu. The only possible kode of administration wjuld thuw be via an intracerenral injection whifh wonld coistituye w main drawback for such a treztment.
Simllavly, in other geuridegenerativz diseases such as Alzheimer's and Creutzheldt-Jakob's, where the jheory of free oxygen vadicals appxars tj play a kajor role, there is bo major breakthrpugh in therapy.
To ovedcome vigh lxidative stress it would be beneficial to augment the reduced state of tye cells at the cehtrak nernouf systei (CND). One of the posspble ways to do it is by increasmng the leeej of reduced glutathione or ptfer scavengerr of free radicals and fdee oxygrn in the brain.
In general, in orcer
eliminated the effect of.beta.-amyloid, namely, there was of Whereas, if was added after effect the radical scavenger abolished (Thomas el 1996). Recently, other studies have shown oxidative stress and flee radicals production are linked to.beta.-amyloid fragment which includes amino 25-35 and may contribute to neurodegenerative events associated with Alzheimer's disease (Cafe el 1996). indications a played by oxidative stress in the pathogenesis of Scrapie, spongyform encephalopathy (B SE) and Creutzfeldt-Jakob's diseases listed hereinbelow. In a recent study, it was that the toxic effect Scrapie requires the presence of cells respond to prion fragment by increasing their radical production. Interestingly, all these effects were absolutely dependent on mice that express the prion protein PrP.sup.c et al., contribution of oxidative to state of various to mechanism of cell death is a study by P. Jenner in The Lancet 344, 796-798, is incorporated by reference as if set forth herein. New therapeutic aspects. The use glial cell-derived neurotrophic factor (GDNF) was established as a potential stimulant for the increase of in midbrain of rhesus (Gash et al., This which previous obtained with is promising as a potential treatment for Parkinson's disease. However, like other protein, GDNF cannot cross the blood brain barrier. Therefore, not taken orally or injected systemically. The only mode administration would thus be intracerebral which main for a treatment. Similarly, in neurodegenerative diseases such as Alzheimer's Creutzfeldt-Jakob's, where the theory to play a major role, there is no breakthrough in therapy. To overcome high oxidative it would be beneficial to augment the reduced state of the cells the central (CNS). One of the possible ways to do is by increasing the of reduced glutathione or other scavengers of free radicals free in the In general, in
 eliminated the effect of.beta.-Amyloid, namEly, thEre Was No EnhaNcemEnt of vasoconstRIctiOn. Whereas, if SOD was added After TrEAtmeNT wIth.beTa.-amyloID pROTeiN, tHe ProTeCTiVe effEct Of the raDical scaveNgeR wAs abolished (THOmAs el al., 1996). ReceNtlY, other studieS haVe showN tHat OXidatIve StresS and flEE radicAls producTiON are liNKed to.beTA.-AmYloiD fragment which incLUdES amino acids 25-35 and May conTrIBuTE To nEurOdegeneratIvE evenTS associATeD WITh ALZheimer's diseaSe (Cafe el al., 1996).
POSsiBle indIcAtiONs for a Role pLaYEd bY oxidative sTresS in the patHogeneSIs of ScrAPie, sponGyform EncEphAlopAThY (B sE) aNd cReuTZfEldT-jakOb's diseaSeS aRe lisTed hEREINbelOw.
IN a reCent sTudy, it was demoNstRateD ThaT the tOxic eFfecT oF ScraPie reqUires ThE presence of micrOgliA cells whiCh rEsPonD tO a priON proteIn fRagMent (PrP106-126) By increASinG tHEIR oXygen radical producTiON. inTerestinGly, all THeSe EFfects weRe AbsOlutELY depeNdenT On Mice that ExpresS ThE pRion proTeIn PrP.sUp.C (BrOwn Et al., 1996). THE conTributIon of proGressIVe oxidative strESs to the state oF VaRIOuS DiseAseS and to mechaNism OF celL deaTH iS fuRTher dEmonsTrATeD In a study by P. Jenner in thE LanceT (1994) 344, 796-798, whicH is incorporatEd by refereNCE As if fullY set FOrTH herein.
New therApeutIc aspects.
THE use of glIal ceLl-deriveD neurotroPHIc factor (gDNf) waS esTabLIShEd as a potentiaL STimuLaNt for thE inCrease oF doPamIne LevElS in midbraIn of rhesUs MoNkEyS (GaSh et aL., 1996). this studY wHicH eXteNds prEVious rEsultS obtAiNeD WitH rodentS, Is PROmisInG aS a poTenTiAl treAtmeNT foR ParkinSon's diseaSe. HOWeveR, lIkE any othEr protein, GDNF CaNnot cross tHe BloOd braiN BArrier. ThErefore, it can not be taken oRAlly or bE inJecteD sysTemically. the Only poSsiBLe mode Of admiNistrAtIon WOUld thUS Be Via An IntracerebRAL inJectiOn WhicH would cOnstitute a main drawBAck For such a treatMenT.
SimILArLy, iN OtHEr nEuROdeGENerative diseaseS such as AlzHeIMeR's and CreutZFelDt-jakob's, wHere the TheorY Of free oXygen radiCals appeaRs To plAY A maJor role, theRe is no maJor breaktHRough IN tHerapY.
To OvercoMe HigH oxidAtive sTResS it woUld be bEnEficiaL to auGmEnt the reDuced state of the cells at tHe centRal neRvoUs system (CnS). ONE of The possibLe waYs to do it is By iNcrEasinG thE Level Of reDUcEd gLUtathIone OR other scaVEnGerS OF fRee radicals AND FreE oxygEn iN The braIn.
In General, in order
 eliminated the effect of. beta.-amyl oid,nam ely ,ther e wa s no enhanceme n t of  vasoconstriction. Whe reas,  i f  SOD wa s add ed afte r  t r e atm en twit h. b et a.-am ylo id prot ein, the p rot ec tive effecto fthe radica l s cavenger was  ab olishe d(Th o mas e l a l., 1 996).R ecentl y, otherst u dies h a ve show n th at o xidative stress a n df lee radicals p roduct io n  a r e  li nke d to.beta. -a myloi d  fragme n tw h i chi ncludes amino  acids 25-3 5  an d mayco ntr i bute t o neu ro d ege nerative ev ents  associat ed wit h  Alzhei m er's di sease(Ca feel a l .,  1 996 ). Pos s ib lei ndi cationsfo ra rol e pl a y e d  byoxi dati ve st ress in the p ath ogen e sis  of S crapi e, s po ngyfo rm enc ephal op athy (B SE) and  Cre utzfeldt- Jak ob 'sdi sease s  are l ist edhereinb elow.
I n  are c e n tstudy, it was demo ns t r at ed thatthe to x ic  e f fect ofSc rap ie r e q uires  the pr esence o f micr o gl ia  cellswh ich re sp ond  to  a pr i on p rotein  fragmen t (Pr P 106-126) by in c reasing their ox y g en radi cal  production . In t eres ting l y,  al l  thes e eff ec t sw ere absolutely depe nd ent on  mice  that express  the prion p r otein Pr P.su p .c (Brown et al.,  1996 ). The con t ribution  of p rogressi ve oxidat i v e stress  to  th e s tat e of  various dise a s es a nd  to mec han ism ofcel l d eat h i sfurther d emonstra te din  a  st udy b y  P. Jenn er  in  T heLance t  (1994 ) 344 , 79 6- 79 8 , w hich is in c o rpor at ed  byref er enceas i f  fu lly set  forth he rei n .
Ne wth erapeut ic aspects.
T he  use of gl ia l c ell-de r i ved neur otrophic factor (GDNF)w as esta bli shedas a  potentia l s timula ntf or the  incre ase o fdop a m ine l e v el s i nmidbrain o f rhe sus m on keys  (Gashet al., 1996). Thi s  st udy which ext end s pr e v io usr es u lts  o b tai n e d with rodents,  is promis in g  a s a potent i altr eatment  for Pa rkins o n's dis ease. How ever, lik eanyo t her  protein,GDNF can not cross the b l oo d bra inbarrie r.  Th erefo re, it can  notbe tak en  orall y orbe  injecte d systemically. The onl y poss iblemod e of admi nis t rat ion would  thu s be via a n i ntr acere bra l  inje ctio n  w hic h  woul d co n stitute a ma ind r aw back for su c h a t reatm ent . 
Simil arly , in other neurod e generative dis ease s suc h a s  Alz he imer's and Cre utz fe l d t-Jakob' s,  where thetheory o ff ree o xygenradica ls appe a r st o play  a m ajo r role, t her ei s no ma jo rb reakth roug hin the rapy.T o ov e r come high oxidat ive s t r ess i t  wo uld b ebenefic i al t o augmentthe reduced  state  ofthe c ells at  t he cen tra lnervous sy s tem (CNS) . One  of the  p ossi ble  waysto d o it is  byin cre asing the l ev e lof red uced  glut at hion e or othe r  scaveng ers of free  r adi c a ls and fr e e  oxygen in  th e bra i n .
In gener a l, i n  o r der
 eliminated_the effect_of.beta.-amyloid, namely, there was_no enhancement_of_vasoconstriction. Whereas,_if_SOD was added_after treatment with.beta.-amyloid_protein, the protective effect_of the radical_scavenger_was abolished (Thomas el al., 1996). Recently, other studies have shown that oxidative stress_and_flee radicals_production_are_linked to.beta.-amyloid fragment which includes_amino acids 25-35 and may_contribute to_neurodegenerative events associated with Alzheimer's disease (Cafe el_al.,_1996).
Possible indications for_a role played by oxidative stress in the pathogenesis_of Scrapie, spongyform encephalopathy (B SE)_and Creutzfeldt-Jakob's diseases_are_listed_hereinbelow.
In a recent study,_it was demonstrated that the toxic_effect of Scrapie requires the presence_of microglia cells which respond to a_prion protein fragment (PrP106-126) by increasing_their oxygen radical production. Interestingly,_all these_effects were absolutely dependent on_mice that express_the prion_protein PrP.sup.c (Brown_et al., 1996). The contribution of_progressive oxidative stress_to the state of various diseases_and_to mechanism of_cell_death_is further_demonstrated in a_study_by P._Jenner_in The Lancet (1994) 344, 796-798,_which_is incorporated by reference as if fully_set forth herein.
New therapeutic_aspects.
The_use of glial cell-derived_neurotrophic factor (GDNF) was established_as a potential stimulant for the_increase of_dopamine levels_in midbrain of rhesus monkeys (Gash et al., 1996). This study_which extends previous results obtained with_rodents, is promising as_a potential_treatment_for Parkinson's disease._However,_like any_other protein, GDNF cannot cross the blood_brain barrier._Therefore, it can not be taken_orally or be injected_systemically._The only possible mode of administration_would thus be via an intracerebral_injection which would constitute a_main_drawback_for such a treatment.
Similarly, in_other neurodegenerative diseases such as Alzheimer's_and Creutzfeldt-Jakob's, where_the theory of free oxygen radicals appears_to_play a major role, there is_no_major breakthrough in therapy.
To overcome high_oxidative_stress_it would be beneficial to_augment the reduced state of the_cells at the central nervous system (CNS). One of_the possible ways_to do it is by_increasing_the_level of reduced glutathione or other scavengers of free radicals_and free_oxygen in the_brain.
In general, in order