╨╧рб▒с>■  46■   3                                                                                                                                                                                                                                                                                                                                                                                                                                                ье┴'` Ё┐Rbjbjы╚ы╚ ?$ЙвЙвR      дддддддд╕╝╝╝╝ ╚ ╕╜ ╢рррррррр< > > > > > > $s h█ jb д╥рр╥╥b ддррw ь ь ь ╥·дрдр< ь ╥< ь ь ддь р╘ ▓0|7╩╝╠ ь ( Н 0╜ ь Eт Eь Eдь <рДd^ь ┬L─рррb b т ррр╜ ╥╥╥╥╕╕╕╝╕╕╕╝╕╕╕дддддд     Dr. Barry Boland writes: УThis year I was very fortunate to be selected as the joint recipient of the annual Peter Carlton Jones Memorial Award for research on Niemann Pick Disease. When notified about the award, I was very excited and booked a trip over from Dublin to this yearТs annual meeting in Telford. It was my first time attending the NPDG (UK) meeting, and also my first experience meeting family and friends of patients with NPD. Being a research scientist whose research is mainly confined to a laboratory, the meeting offered a great opportunity for me to see patients with NPD first hand and experience the warm community spirit and strong support amongst attendees from all over the UK. The meeting was very well organized, with internationally renowned guest speakers and entertaining social events, where I had the opportunity to overcome my snake phobia! I am thankful to everyone I met during the weekend, whose helpfulness and enthusiasm about my research, encouraged me to continue working in NPD research. Best Wishes, BarryФ Dr. Barry Boland - Winning Abstract for Peter Carlton Jones Memorial Award I am a post-doctoral researcher who obtained my PhD in the field of AlzheimerТs disease at Trinity College Dublin, and spent over two years working at the Nathan Kline Institute, New York, on a project that investigated the role of autophagy in the neuropathology of AlzheimerТs disease. I worked with Professor Fran PlattТs group at the University of Oxford from 2005-2008, on a project that determined whether mechanisms causing neurodegeneration in Niemann Pick Type C1 (NPC1) disease share common features with the neuropathology of AlzheimerТs disease. I have continued my research on NPC1 since moving to University College Dublin as an independent scientist. From my research on NPC1 disease, I have found that neurodegeneration in the NPC1 brain shares similar hallmarks with degenerating neurons from an AlzheimerТs disease brain. While these two diseases affect people at polar ends of the age spectrum, they are comparable when the extent of autophagic dysfunction in both diseases is taken into consideration. Autophagy is a process where cells Уself-eatФ parts of their own constituent, to dispose of waste material or obtain essential nutrients in times of starvation or stress. Cells continually use autophagy as an economical way to recycle old parts of itself into new parts. During autophagy, cells engulf regions of themselves into vesicles, known as autophagic vacuoles (AVs), which are delivered to lysosomes where the contents are digested. I have found that the progressive accumulation of lipids in the NPC1 brain impairs the ability of neurons to process AVs, which results in stress-related degeneration caused by the excessive build up of these undigested organelles within neurons. By analysing brain tissue from mice with NPC1, I have found that NPC1 mice as young as 3 weeks old have abnormally high levels of unprocessed AVs in their brains, which persist throughout their lives. Considering mouse models of NPC1 do not develop neurological symptoms associated with the disease until they are older than 3 weeks, it is likely that dysfunctional autophagy precedes and may contribute to neurodegeneration in NPC1 disease. In addition to neurons, liver cells from NPC1 mice contain abnormally high amounts of unprocessed AVs, indicating autophagic pathology is involved in other organs as well as the brain. In healthy neurons, AVs are processed by lysosomes with such high efficiency they are rarely seen. When neuronal autophagy is impaired in NPC1 brain tissue, waste products accumulate inside AVs, forming toxic substances. I have found that the metabolism of a protein involved in AlzheimerТs disease, known as the amyloid precursor protein (APP), is also perturbed in NPC1 disease. Mice with NPC1 have higher amounts of APP metabolites in their brain compared to normal mice, due to an impaired rate of AV digestion by lysosomes. From data obtained in my research, I have found a correlation between the accumulation of AVs and increased amounts of APP metabolites in NPC1 brain tissue. Interestingly, both of these hallmarks co-exist in AlzheimerТs disease, which indicate that certain features of neurodegeneration occurring in NPC1 and AlzheimerТs disease may share a common underlying mechanism. Unlike AlzheimerТs disease, which affects people late in life, the rapid rate of cognitive decline affecting young patients with NPC1 is due to a progressive build up of undigested substances in neurons, beginning from birth. Our results suggest that the storage of AVs and APP metabolites in neurons is a driving pathogenic feature of both NPC1 and AlzheimerТs disease. Preliminary evidence from my research indicates that pharmacologically reducing the amount of lipid storage in NPC1 mice, using miglustat, reduces the intraneuronal accumulation of AVs and APP metabolites. I hope that by continuing my research into understanding how excess lipid storage in NPC1 affects autophagy and APP metabolism, I will be able to develop new therapies aimed at alleviating the storage burden and improving cell function in NPC1 disease. БК] ^ ` a     4 U ^ f ЛМPQRЁ▐╨┐╨┐╨┐╨┐╨┐▒ж▒ж▒ЩПЩПЩПЩПЩЖВh9╡h░Rч5БCJaJh░RчCJ^JaJh^ugh░RчCJ^JaJh░Rч5БCJ^JaJh^ugh░Rч5БCJ^JaJ h^ugh░RчCJ^JaJmH sH h░RчCJ^JaJmH sH #h^ugh░Rч5БCJ^JaJmH sH h░Rч5БCJ^JaJmH sH   f ЛМOPQRўўяъўўўўўўўўўъъшgd░Rч$a$gd░Rч$a$gd░RчR¤= 0P&P 1РF:p+О░В. ░╞A!░"░#РД$Р%░░╨░╨ Р─ЖЬ@`ё @ ░RчNormalOJQJ_HmH sH tH DA@Є бD Default Paragraph FontRi@є │R  Table NormalЎ4╓ l4╓aЎ (k@Ї ┴(No ListR$    f  Л М OPQTШ@0ААШ@0ААШ@0ААШ@0ААШ@0ААШ@0ААШ@0ААШ@0ААШ@0ААШ@0ААШ@0АААШ@0АААШ@0АААШ@0АААШ@0АААI╚00АRRR   СsяТs iюУs▄ФsЬlЁХs4эЦs▄"юЧs|ёШsdўЩs№¤,║║╕╕╞T 3╝╝!!┬╠╠T9*Аurn:schemas-microsoft-com:office:smarttagsАplaceАB*Аurn:schemas-microsoft-com:office:smarttagsАcountry-regionА8 *Аurn:schemas-microsoft-com:office:smarttagsАCityА9*Аurn:schemas-microsoft-com:office:smarttagsАStateА=*Аurn:schemas-microsoft-com:office:smarttags АPlaceNameА=*Аurn:schemas-microsoft-com:office:smarttags АPlaceTypeА 45║ NW!+fo' 0 | Е ┬ ╠ ╫ ┌ Х Ш ж й Ж П 4 7 D N а г ¤ JMў·(9<┤╜T^ d T3T хcRB А I tfнЖ+О9╡l┌░RчQT @АQQ╪бQQRp@  Unknown            GРЗz А Times New Roman5РАSymbol3&Р Зz А Arial"qИЁ╨h▒К┘Ж▒К┘ЖJ $J $!ЁДxгВА24HH2ГqЁHP)Ё ?ф                     ░Rч2  DrMichelle ScobieMichelle Scobie■ рЕЯЄ∙OhлС+'│┘0|РШд░╚╘рЇ  8 D P\dltфDrMichelle Scobie Normal.dotMichelle Scobie1Microsoft Office Word@@Оь|7╩@Оь|7╩J■ ╒═╒Ь.УЧ+,∙о0 hpШаи░ ╕└╚╨ ╪ чф Niemann-Pick Disease Group (UK)$ H' Dr Title ■   ■    !"■   $%&'()*■   ,-./012■   ¤   5■   ■   ■                                                                                                                                                                                                                                                                                                   Root Entry         └Fр'┼0|7╩7АData             1Table    WordDocument    ?$SummaryInformation(            #DocumentSummaryInformation8        +CompObj            q            ■                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                           ■       └FMicrosoft Office Word Document MSWordDocWord.Document.8Ї9▓q