, .. . . - . -. ,, 5 5 5:55
5. ,.. . 5-5 - , - . 5. . T. 1:.1'.1 , a; 5. ,. I WW .- 1 ,5 ..,I. ,I ,5 ,- y 5. i,,-,,,t{;, 5:55.; 9:5,. 97.51, 4: "nab. ,5- g1}, 35:, r v. g, If , D , [ngnyh
W . _ . ., ,. . , 1. 1, J, ,.-,.'. gets-'2 -r fwqu. 25-, (3.1. .~'~";I-, 5 1,19%. ~~=1,'.::::1,51I{"}i. irqf'awf' 5' . 315:5: 1,1,5: hath-13"" . 7s1..'_ 55-15, .ib..i1zi.,i.. sq,,.'."-s ?;*..s1~;55 3:513 .,', 1.; ,-'I
OXIdatYe .Stress an .e".0 "g ' genesis of the disease. Prevention is the key to AD and ecause ox 3.7.:56165. k; . g Qs-3:53:31."
DiStIngUIShlng Fact from F'Cton dative damage is present early in the disease. antiOXIdant therapy has 15,1 33.15.- Witt-5., 5: .I, 1"..217353
Neurodegenerative diseases have three common features: Imito, thepotjentital of (IslmtIiI/IigliJ gufgvgggg; 52,}: 'irzgiijgi: 8;: $.31: 15-,- _ _-  15'_ . '1 g]?
' ' n, increased oxidative damage and accumulation o aIntioin an s an o , . :3. 5:33;: : I I f ',; {.5}: j: E 5,;
gagggriizlliiiiigigo All three are intimately related, with failure of the high risk for AD before the neurodegenerative changes OCCUr 5.55., 5.":- 5; ,5, I: st-'5;
clearance mechanism for abnormal proteins often being a primary 1.45 pm Question and Answer Session t5- . ._ 1, .
event. It is important to study these events in humanIpostmortem - . . iI , I1 11. : ,. 3551 . 3,3,,
material (although the conclusions drawn are necessarily limited) and in 1.55 m Dr J Timothy Greenamyre, University of Pittsburgh 151}? . . ,, 1, .. 3??
animal models; studies on cultured neurons may give artifactual results. I p. . "Convergent Pathways to Parkinson's Disease" 1 '_  ' 1 5. established in the memory 0f i, . y ". .1 .233;
This will be illustrated by studies of dopamine tOXIcity and GSH levels. . 2. 5:31.51 .I, ., 1 N ff .\ 311.3%, .
' d A r Session Rarely, Parkinson's disease (PD) may be caused by single gene 1,139'5- . I Anna S_ a 5:55 _ ,1,st
9:30 am. Question an nswe mutations or environmental exposures, but most cities areflikely n:- .,';I_  1,, .5 w 1 ,",5:"_i".
. , , . . lated to individual genetic susceptibilities and a lelme 0 enV'Iro ' 'ijZK 5': " 3-, ' {gt-3.35;!
9140 am. Dr- 'W'" FrldOV'Chi Du University . . dozen enetic loci have been described .55; 11g .5 . - - - _- 11 ' :11. A . .,
"The Biology Of Superoxide and a Novel Aetwlty for annihifiloerzgiiiisalnZfl2)??ilie::egyenes hgve been identied. Despite the aLII ; ' ,., Odeatlve Stress In Aging psmvii
the CU'Z" SOD" multiple genes and potential environmental causes of PD, there :5 L1 II'T l and Age-Related 75,31,145; 52? '3
' dim" t "3 very efuent Cindi/Sis Of he dismmati'on 'Of sui increasiing erigence iainaaiigiiitit iridpfnilgg'ni.Eihyasiiinciio'ns 1:? i-I-zi. Neurodegeneratlve Disorders 5 91",}
- D1 catal es the bicarbonate-dependent perOXIdatIon 0 involve . InCU '09 PTO 8' , , I. 1. .' wI;;;1,:,.,,.I is? ___.,,II.II .S f 1 I,
gii/rejrggesuigrates. Tiize mechanism of the peroxidations can,be de- both of which may be related by OXIdative stress. . .-"- I g, 1 a .41..,=.f3-".
. actions a _ d , a E-Cu(ll) + H202 e E.Cu(i) + 2H + 02-; . _ I . 3, ,. .. 93%
fptgiiilr): H202 (9)I(E_();u((l)g) + H20; (c) E-Cu(l)O 69H , E-Cul|)0l(-Il 2:40 pm. Question and Answer Sesswn ,3 I s1..... . . , SPEAKERS ;:.- ,1 .3};
_ m + OH'. The bound oxidant produced by reaction (b, an . . . . San LG I; . 5 L5, 5131 3;
siioEwgtiii s)everal possible forms in reactions (c), then oxidized C02 to 2:50 pm. Dr. Don W, Cleveland, Universlty Of California, as L0 :Jl . -,,,.I B H III e 1.", 1 5:
(:03; as shown in reaction (d). (d) E-CU(")OH + C02  5'0) + OH B'ego G wth and Death' Neurolaments, 4-5 O 3'  Leg? '2 arry a [W 351 " i" .i
+ C0569 H + C035. Surprisingly it is C02, and not HCOI3, that Mot?" AIIjezronGeIrIcriI II . .2 >5 CI 11}; 5.4 . I, Irwin Fridovich 5.31115557' 5.,
becomes oxidized to the 003$; that then diffuses from the active site SOD an DU 9 E g 8 35*. 5:3, .3; I I1}, f. a
and oxidizes diverse substrates in bulk solution. CQafIhas a standardI ALS is characterized by premature death of motor neurons. _QC) 3 L0 I. 5):? Earl R. Stadtman is..#.:"'1.'?.1.r',1,1.93i
recIlox pgteni-iaolOfJ':n:ri:igLrltledsbeTegiii/r: gzmggtingveblgro, Mutation in superogideIdIitsmutasIZtSQEJIBSIcIaIItggz saiiiiigeniersfgicr: 0 g g 1. 111, "f2; 171,55, , William R. Markesbery f. #4.,
miieut an :smcei I . , - throu h an acquire oXIciyunre , . -I 6-- 5- , '1 3:124:53
is produced in significant amounts in cells remains to be demonstrated: yokesg mutant-mediated damage to mitochondria only Within affected 5 EC >_ .sftiiia, J. Timothy Greenamyre (i-1. 15:533.:
. - tissue, which in turn triggers caspase mediated cell death. Toxmty is 4: .5 x R, If . D W Cleveland i253? 55:73:33: _
10:25 a,m. Question and Answer Sesslon noncell autonomous. requiring mutant soot IactionIon axonal ele- 5 >5 - i'ijf-cg'i - on . ,5, ,I, 51-31131:
' ' fH lth ments including neurolaments, but also reqUIring action Within astro CD I: g ugh-j, , ,I ', 34:11:35 I. ', ,.;
10-35 a m Dr. Earl R. Stadtman, National institutes 0 ea . . . th development through stem cell E .15 . . v:-.'1.:.'-1,---",1: :;.,k5,,,5.,;. gt
I i I "Roles of Bicarbonate Buffer Apoptosis and Carbon/ cytes and microgiia. supporting erapy 1: 2 "'5, 93%;: {:18 N. . :~ .1 ,1, 4
Nitrogen Deciency on Metal-Catalyzed Oxidation of replacement of non-neuronal ce 5. g g .E F, 51,50, Friday, April 15, 2005 5,53%? ,2.
Proteins and Lipids" 3:35 pm, Question and Answer Session 0) E 6 $691: i355 II,;:;.f>5 :
. .. . I . _ Q :3 _I Q, -.iI -.'-,_},,.":1.;1:I:. F5345 '25:- .I i,- {1
The OSSIbilit that loss of apoptotic capacity contributes to age I . _ , I 5 3 .,Ii . , I ctr55.,
sisssis ii .5 5 '1 Department of Chemistry
in that inhibition of apoptosis in acute promyelocytic ce 5 ea 5 o a : ,,;,'.,I..,,_1I,,55;;:1.1 , I . . , i... .,. 'I 1:
Sugbstantial increase in the level of oxidized proteins. Metal-catalyzed O I?i1l} UanerSlty Of Kentucky if? .-1s~;;.- 1? . I.
oxidation of LDL is greatly stimulated by the presence of bicarbonatel, :5, 5-1-53 31,15,113: Lexington KY 40506-0055 53",, 'J-I a;
002 buffers at physiological pH. Replicative senescence inblf. i'OIi 4T,,;j::;":35;{,I-I,K .  15,313. 1.;1 .51 .
' duced b either carbon or nitrogen starvation leads to su san Ia . . in .html , . 1; -;"I:.:J1;'3_I,,I ..,-,,I,, 95' . 51.3: . 24;; . 5,5: -$5
in the levels oroxidized proeinst , "iii?WWW-them'he"flii'miifwelgi e  , .555. 1:111 '- ' 5' :- 351$ .1 Wm-5:: .
,, .. 51,-... I5... ,, 55:5: 1-1 ,.?i~1;:..';s-~,;I.";ij,. 41.1' . 55553,. ; 1:51 , fags? ;'#~3 .s'";1_:i-.,,'s=1,.,i~~*~zgm-55,, ..?:::1..,;,..,;I 35'9: 531:1- ,1'.1,f:-' 1,5,: _5-1551 - 55: :5'1';'7T.i.:;.!$,:..3:":.- 5.2.1: ,'
5 4;ng .ri xii :. ZS-t. . 3M . . , . 5 ., , . m. 5 a, .;, .3 . . v. , , . 5, . ...t mm?) m; .. W . 55* i v. . ti 1. in. 1 1w: . 13w. 3&3 J o. -v
5.; 5 as? ,5; ,3. ,~ {.2 g1 5, - 1. E1: ,5, 51%51555 ,, 1.155.. 52.55 5 1i: .- $51: 5151 'ssis 55,. 5,55; 5. ,ksx
is! 5-; 5 :5; 25: 35}? ";L1Vu~a\3v~ .,.?d 5555 5'21.1352-1 ., 55 1.215215. 5.,gsig,*ss"i""f"vv 1.525, 3 531131;: 1'.,.'; " ;,,;;ioi5:f; A' 55"" 32. 3.1511" trail
5,f'i-jif e,;5es, 5,1: 5&55i5. 5.495.9"355553355155 55555 r1555 5*. 5 ts 55.555551:
33554: :5 55$. 5., .1 A: .5, .-' i 55:? 5W ' x .155 . mailed .55 5: 1555,5131. 5,, :1. 5-1.: ' i ,5 . 2:51: 1.15:. 5:515 5.51,.
5W4 #9 5:555, g-{~53  53:9; W37: Pasf' :Z':.1.":"Er.:t:;: 2551' 5;-."-"s 35? .1. ' 5.955;; It $61.;t ,3. 41-6.), - :,.,,,,:1'1i.1,,,:::.,5,_e_5e;,, mgg 2;, R #55:: 525:5? gm . -:5?-,fs,.~3.1.1.~.-1'j .g. as}, .1991,- ,-,.,.-3;1,;1 .9I;;.,.15I,11s.=;.35.1.13"... ,-1,.;I - 1.9., ,1 3,,55 ,1 tv- .531; .-
' 5. z '. . 5" -. .-I1; ,9, . " '5,  :. : -,II.:=;-.,I,~n..1.,.,1). {51,151,} . - '1, ' 1 , .55.?! .151, 5:? 1-I-_I},;. , :11,,-,I,I.Ii-1s;x;~..,,1;.g -.~.I, mg '5. 35,1 "(3.. 333-: .4. is? . .I-IiI 5,; 1,1:1. 35 :5- 1'.v',,:;,$e -' 91w '1  : - -- 1 ' W ' --  '  
-.- 4 W: .. it? ...,..$,1.;g..lr?_ o, fiYii-yt 1: if." t 1'. at. h'vi" are... .1 '1: ,1 .i 193 >'.;- ""E - .13.?E- .- '. 3i; 1.! -  - ' , ~ -1
s." 54,313.35:51.52551 ;. 57". If? 112. .51 :1" r; 5 1 '1' 1 5.. 1 , - 11 1