gotz ittner nature rev neurosci 9 532 2008 1 3 28 11
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  1. 3/28/11 !"#$%&'()*+&,')-'.!/0' !"#$%&#'$()*+%,-./"+/%)0"-1)2-3%/)2-4/&%)5-)56/)7&+$+, ' !"#$%&'(&)#!*"+#,&-.(/( & 12%"3+&&)4 ’ ,'54)-+,,)4'%"*'/#4+36)4 ' 8$%'535/)0-")2/1-"9)81:#+"1/$5% ) #$4);/3"-&-(+,#&)*+%-"4/"% ' 7)862+4"'1%&#-)4"#%'79$:),#8$')"'.%$#&#%&'!&;2+#$+4<,'/#,+%,+0 ' 5%62=%9,'6)'>4+%6$+"6 '' ' 0*1&-23$45& • ?++*'@+A+4'%"#$%&'$)*+&,')-'62+'*#,+%,+B':%4C38&%4&9'62),+' @%,+*')"'62+',:)4%*#3'D+4,#)"')-'62+'*#,+%,+' • ED+"'#"'%"#$%&'$)*+&,B'62+',))"+4'64+%6$+"6'@+F#",'62+'$)4+' &#G+&9'62+'3)F"#CD+'#$:%#4$+"6,'%4+'#$:4)D+*' • >%4F+C"F'!H'%I+4')62+4':%62)&)F#+,',+6'#"B':%4C38&%4&9' :2),:2)6%8'%"*'?.>':%62)&)F9B'*)+,'")6'4+,38+'3)F"#CD+' #$:%#4$+"6,' • 1)$@#"%C)"'62+4%:#+,'%4+'&#G+&9'6)'@+'4+J8#4+*' • 76+$'3+&&'%"*'#6,':)6+"C%&'-)4'!/' !"#$%&'()*+&,')-'!/ ' Gotz & Ittner., Nature Rev Neurosci 9, 532 (2008) 1

  2. 3/28/11 6$37#+&'28*+&9:;;*55*5<&927*&=>#7?+*5& • /+K"+'62+':%62):29,#)&)F#3%&'4+&%C)",2#:'@+6=++"'!H'%"*' 6%8' • /+6+4$#"+*'62%6'6%8'#,'"+3+,,%49'-)4'!HL$+*#%6+*'6)M#3#69' • N+A+4'%::4+3#%C)"'62%6',)&8@&+'-)4$,')-'!H'%"*'6%8'$%9' :&%9'34#C3%&'4)&+,'8"*+4&9#"F'3)F"#CD+'*9,-8"3C)"O,9"%:C3' 6)M#3#69' • P*+"C-9'$%"9':)6+"C%&'")D+&'64+%6$+"6,'&#G+'!H' #$$8")62+4%:9B'@86'64%",&%C)"%&'#,,8+,'%4+'$%"90'=2+"'6)' %*$#"#,6+4B'3)",+J8+"3+,')-'G+9'*#Q+4+"3+,'#"'28$%"' D+4,8,'4)*+"6'#$$8"+',9,6+$B'+63R' @+3$3;#+&A"3#+&/35#??23$47*$45& 2

  3. 3/28/11 Not all treatments work in mice Intervention Effect on Pathology Effect on Cognition Nicotine Exacerbated tau Not determined Melatonin No improvement No improvement Resveratrol No improvement No improvement IGF1 No improvement No improvement High fat diet No change No change Copper Exacerbated Aß & tau No change pathology ! 2 agonists No effect on Aß, slight No improvement reduction of phosphotau Blueberry diet No improvement No improvement Lithium No effect on Aß pathology; No improvement Lower phosphotau !4+'!H'>2+4%:#+,'>))'S#A&+OS%6+'-)4' !/T ' @2$;*"$5&B34.&'28*+5& • S%3G')-'3)"3)4*%"3+'@+6=++"':4+3&#"#3%&'$)*+&,'%"*'28$%"' 3&#"#3%&'64#%&,'U=4)"F'6%4F+6,B'=4)"F'$)*+&,B'&%3G')-'D%4#%@#&#69' %$)"F'#"*#D#*8%&,'#"'62+'$)*+&,B':%C+"6,'+"4)&&+*'6))'&%6+B'+63V' • W8$%",'+"4)&&+*'#"'3&#"#3%&'64#%&,'%4+'2+6+4)F+")8,B'=2+4+%,' $),6'$)*+&,'8C&#;+'#"@4+*',6%#",')-'$#3+' – ED%&8%C"F'")D+&'64+%6$+"6,'#"'$8&C:&+'&#"+,'$%9'2+&:'%**4+,,'62#,':)#"6 ' • S%3G')-',8@,6%"C%&'"+84)"%&'%"*',9"%:C3'&),,'#"'62+'$%X)4#69')-' 4)*+"6'$)*+&,B'#"*#3%C"F'62+'$)*+&,'@+A+4'4+:4+,+"6'62+' :4)*4)$%&':2%,+')-'62+'*#,+%,+' • ()*+&,'%4+')-'-!/'%"*'$),6':+):&+'2%D+',!/' 3

  4. 3/28/11 A"#$5+#C2$#+&@.#++*$D*5& • !/'#,'")6'3)$:&+6+&9'8"#-)4$'3&#"#3%&')4':%62)&)F#3%&'+"C69Y' 3)$:&#3%6+*'@9'&)"F':4)*4)$%&':2%,+'%"*')62+4'3)Z$)4@#*#C+,' %"*'%F#"F':4)3+,,' • [584+\'!/'#,'8"3)$$)"' – $#M+*':%62)&)F9'3)$:&#3%6+,'64+%6$+"6' • >%4F+C"F'!H'%&)"+'%I+4')62+4':%62)&)F#+,',+6'#"B':%4C38&%4&9' :2),:2)6%8'%"*'?.>,B'*)+,'")6'4+,38+'3)F"#CD+'#$:%#4$+"6,' • >4+%6$+"6,'%4+'#"+Q+368%&'%I+4'!H'%"*'6%8':%62)&)F9'*+D+&):0' :%,,#D+'#$$8")62+4%:9Y'/W!Y'&#62#8$Y'$+*#3%&'-))*,B'+63R'' • .)38,'"++*+*')"')62+4'*)=",64+%$'6%4F+6,R' -24*$C#+&A#"D*45&E2"&6/& • !I+4'!H'%3CD%6+,'3%,3%*+B'-)38,'"++*,'6)'@+'*#4+36+*'%6')62+4' *)=",64+%$'6%4F+6,R' • 5)6+"C%&'D#%@&+'6%4F+6,' – >%8' – >4%",34#:C)"%&'UW/!1'#"2#@#6)4,V' – ?+84)64%",$#A+4,0'(]'4+3+:6)4,' – P"^%$$%C)"' – !86):2%F9OS9,),)$%&O54)6+%,)$%&',9,6+$' – ?+84):4)6+3CD+',64%6+F#+,' – 1+&&Z@%,+*'%::4)%32+,' • 1)$@#"%C)"')-'62+4%:#+,'#,'&#G+&9'4+J8#4+*' !86):2%F9' 54)6+%,)$+' /#,48:6' P$:%#4$+"6,' _#"%,+O 52),:2%6%,+,' U12P5V' P$:+*+' >%8' P"^%$$%C)"' !M)"%&'' 5%62)&)F9' >4%",:)46' 4

  5. 3/28/11 &6/&&& & &&&&&@2$4"2+ ' Advantages of Neural Stem Cells 1. No ethical debate as does not require destroying embryo. 2. Transplanting neural cells into neural tissue. 3. Can differentiate neural stem cells into neurons, oligodendrocytes or astrocytes. 5

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  10. 3/28/11 ?+:4#&9,#"Z+M:4+,,#"F'?71,'4+*83+' ' !H :%62)&)F9' sNEP NSC side control NSC side Red: A " Green: Tau • e#&&',#"F&+')4'3)$@#"%C)"')-'F4)=62'-%36)4,'@+' @+A+4'D,R'3+&&'%::4)%32T' • 7+&+3C)"')-'%::4):4#%6+'3+&&'69:+''' U7+MB'!:)E'F+")69:+V' • 7%-+'F+"+C3'$)*#K3%C)"')-'3+&&,' • d+F#)"'6)'@+'64%",:&%"6+*' • P$$8"),8::4+,,#)"'4+F#$+"' • ?8$@+4')-'3+&&,'6)'@+'64%",:&%"6+*' • S)"F'6+4$',84D#D%&O@+"+K6,')-'F4%I' • !"9'%*D+4,+'+Q+36,O68$)4,T'' Feng et al., Am. J. AD Other Demen 2009 10

  11. 3/28/11 H$I*5CD#42"& H$5C4:C2$& J2+*& .4%"G'S%.+4&%B'52/' f1'P4D#"+' 54#"3#:%&'P"D+,CF%6)4' (%62+='N&846)"Zg)"+,B' f1'P4D#"+' P"D+,CF%6)40',6+$'3+&&,' 52/' d#32%4*'N)9*B'52/' ()"%,2'f"#DR'U!8,64%&#%V' P"D+,CF%6)40'6)&+4%"3+' 5+6+4'/)")D%"B'52/' f1'P4D#"+' P"D+,CF%6)40'2E7'3+&&,' _+""+62'_),#GB'(/B'52/' f1'7%"6%'N%4@%4%' P"D+,CF%6)40'$#34)d?!' 768%46'S#:6)"B'(/B'52/' N84"2%$'P",C686+' P"D+,CF%6)40':&%,C3#69' g+%""+'S)4#"FB'52/' 734#::,'P",C686+' P"D+,CF%6)40'$)&R':4)K&+' (%4G'>8,;9",G#B'(/B'52/' f1'7%"'/#+F)' P"D+,CF%6)40':4#$%6+,' !3G")=&+*F+$+"6, ' Stem Cell Collaborators Current Lab Former Lab Members Jeanne Loring Mathew Blurton-Jones Salvatore Oddo Debbi Morrissette Stuart Lipton Masashi Kitazawa Antonella Caccamo Michael Sy Kim Green Richard Boyd Grace Stutzmann Michael Sugarman Hilda Coria-Martinez Mark Tuszynski Rodrigo Medeiros Malcolm Leissring Yama Akbari Ken Kosik David Baglietto Lauren Billings Tritia Yamasaki Peter Donovan David Cheng Lani Clinton Eliezer Masliah Nicholas Castello Maya Koike Kris Myczek Kristine Freude Funding KC Walls CIRM Kara Neely Andrew Tran NIH Meredith Chabrier AHAF Adam Pabst Cure AD Tatiana Estrada Jack Reidling Angela Monroe 11

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