{"id":5955,"date":"2026-10-19T09:48:14","date_gmt":"2026-10-19T09:48:14","guid":{"rendered":"https:\/\/phd.hi.is\/doktorsvorn\/doktorsvorn-i-lyfjavisindum-natalia-magdalena-kowal\/"},"modified":"2026-10-19T09:48:14","modified_gmt":"2026-10-19T09:48:14","slug":"doktorsvorn-i-lyfjavisindum-natalia-magdalena-kowal","status":"publish","type":"phd_defence","link":"https:\/\/phd.hi.is\/en\/doktorsvorn\/doktorsvorn-i-lyfjavisindum-natalia-magdalena-kowal\/","title":{"rendered":"Doktorsv\u00f6rn \u00ed lyfjav\u00edsindum – Natalia Magdalena Kowal"},"content":{"rendered":"
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Mi\u00f0vikudaginn 15. jan\u00faar ver Natalia Magdalena Kowal doktorsritger\u00f0 s\u00edna \u00ed lyfjav\u00edsindum vi\u00f0 Lyfjafr\u00e6\u00f0ideild H\u00e1sk\u00f3la \u00cdslands. Ritger\u00f0in ber heiti\u00f0: Leit a\u00f0 lyfjasprotum og \u00e1skoranir vi\u00f0 leit n\u00fdrra lyfja gegn Alzheimers og \u00f6\u00f0rum taugahr\u00f6rnunarsj\u00fakd\u00f3mum. <\/strong>Searching for drug leads and facing the challenges in drug discovery for Alzheimer\u00b4s and other CNS diseases.<\/strong><\/p>\n

Andm\u00e6lendur eru dr. Neil Millar, pr\u00f3fessor vi\u00f0 University College London, og dr. Judith Rollinger, pr\u00f3fessor vi\u00f0 University of Vienna, Austurr\u00edki.<\/p>\n

Umsj\u00f3narkennari og lei\u00f0beinandi var dr. El\u00edn Soff\u00eda \u00d3lafsd\u00f3ttir og me\u00f0lei\u00f0beinandi dr. Thomas Balle. Auk \u00feeirra s\u00e1tu \u00ed doktorsnefnd dr. M\u00e1r M\u00e1sson, pr\u00f3fessor, dr. Sesselja \u00d3marsd\u00f3ttir, pr\u00f3fessor og dr. Philip Ahring, lektor.<\/p>\n

Berglind Eva Benediktsd\u00f3ttir, d\u00f3sent og varadeildarforseti Lyfjafr\u00e6\u00f0ideildar, stj\u00f3rnar ath\u00f6fninni sem fer fram \u00ed H\u00e1t\u00ed\u00f0asal H\u00e1sk\u00f3la \u00cdslands og hefst kl. 13:00.\u00a0<\/p>\n

\u00c1grip af ranns\u00f3kn<\/strong><\/p>\n

Alzheimer og a\u00f0rir mi\u00f0taugakerfissj\u00fakd\u00f3mar eru mikil \u00e1skorun vi\u00f0 \u00fer\u00f3un n\u00fdrra lyfja. N\u00fd tilraunalyfjaefni falla oft \u00ed s\u00ed\u00f0asta fasa kl\u00edn\u00edskra pr\u00f3fana \u00ed m\u00f6nnum. Eftir sem \u00e1\u00f0ur er mikil \u00fe\u00f6rf fyrir n\u00fd og betri lyf vi\u00f0 \u00feessum erfi\u00f0u sj\u00fakd\u00f3mum. \u00dea\u00f0 ver\u00f0ur s\u00edfellt lj\u00f3sara a\u00f0 fl\u00f3ki\u00f0 samspil l\u00edffr\u00e6\u00f0ilegra \u00fe\u00e1tta \u00ed sj\u00fakd\u00f3mum mi\u00f0taugakerfisins kallar \u00e1 fj\u00f6l\u00fe\u00e1tta n\u00e1lgun \u00ed lyfjame\u00f0fer\u00f0. Fyrri hluti ranns\u00f3knarverkefnisins fjallar um skimunarleit \u00ed t\u00f6lvu a\u00f0 lyfjasprotum me\u00f0 tv\u00ed\u00fe\u00e6tta verkun; annars vegar \u00e1 aset\u00fdlk\u00f3l\u00ednesterasa (AChE) og hins vegar \u00e1 nik\u00f3t\u00edn aset\u00fdlk\u00f3l\u00edn vi\u00f0taka (nAChRs). Alzheimerslyfi\u00f0 galantam\u00edn var nota\u00f0 sem samanbur\u00f0arefni, en \u00fea\u00f0 var \u00feekkt sem AChE hindri og auk \u00feess sagt vera j\u00e1kv\u00e6\u00f0ur ag\u00f3nisti \u00e1 nAChRs. S\u00fdnt var fram \u00e1 \u00e1hugaver\u00f0a tv\u00ed\u00fe\u00e6tta virkni galantam\u00edns og tveggja \u00e1\u00f0ur \u00f3rannsaka\u00f0ra efnasambanda, en virkni \u00feeirra allra vi\u00f0 nACh vi\u00f0takana var andst\u00e6\u00f0 \u00fev\u00ed sem \u00e1\u00f0ur var haldi\u00f0 fram fyrir galantam\u00edn. T\u00f6lvuskimunara\u00f0fer\u00f0in reyndist gagnleg og greinir efni me\u00f0 virkni sem n\u00e6r yfir tv\u00f6 \u00f3l\u00edk lyfjam\u00f6rk. \u00cd seinni hluta ranns\u00f3knarinnar var virkni galantam\u00edns, vareniclins og nokkra mi\u00f0taugakerfislyfjaranns\u00f3knaefna (ABT-089, ABT-594, ABT-894, RJR-2408 and SIB-1508Y) \u00e1 nAChRs k\u00f6nnu\u00f0 og borin saman vi\u00f0 ni\u00f0urst\u00f6\u00f0ur fyrri ranns\u00f3kna. Ni\u00f0urst\u00f6\u00f0ur gefa til kynna a\u00f0 me\u00f0 \u00fev\u00ed a\u00f0 nota n\u00fdjustu \u00feekkingu og bestu in vitro a\u00f0fer\u00f0ir f\u00e1st mun n\u00e1kv\u00e6mari ni\u00f0urst\u00f6\u00f0ur um virknipr\u00f3f\u00edl efnanna en fengust \u00ed eldri ranns\u00f3knum \u00fear sem efnin sem valin voru st\u00f3\u00f0ust ekki kl\u00edn\u00edsk pr\u00f3f. \u00dea\u00f0 er lj\u00f3st a\u00f0 takmarka\u00f0ur skilningur \u00e1 starfsemi heilans og samspili hinna \u00fdmsu ferla sem lei\u00f0a til taugahr\u00f6rnunar, \u00e1samt \u00fev\u00ed a\u00f0 ekki eru til g\u00f3\u00f0 forkl\u00edn\u00edsk l\u00edk\u00f6n me\u00f0 forsp\u00e1rgildi, gerir lyfja\u00fer\u00f3un gegn \u00feessum sj\u00fakd\u00f3mum s\u00e9rlega erfi\u00f0a.<\/p>\n

Abstract<\/strong><\/p>\n

Alzheimer\u2019s disease (AD) and other central nervous system (CNS) diseases continue to be a challenge for drug discovery. Drug candidates often fail in the latest stages of clinical testing leaving the society in continuous need for new medications which allow for a better management of these disorders. It is becoming apparent that the complexity of CNS diseases requires multi-target therapies. In this project, an approach in finding dual active compounds towards acetylcholinesterase (AChE) and nicotinic acetylcholine receptors (nAChRs) using computational chemistry was taken. Galantamine, an AD drug, was used as a reference compound and was known as a positive modulator of nAChRs as well as AChE inhibitor. Two previously unknown dual active compounds were found. However, they together with the reference compound galantamine, unexpectedly were shown to inhibit the nicotinic receptor. As a tool, computational methods showed to be useful and capable of selecting new entities with activities across two targets. Further, activity at nAChRs of galantamine, varenicline and a few former drugs candidates (ABT-089, ABT-594, ABT-894, RJR-2408 and SIB-1508Y) for CNS diseases were investigated and compared with previous results from the literature. This study showed that with increased knowledge and substantially improved in vitro methods, better characterization of compound activity profiles can be achieved. Lack of quality data in the early studies probably contributed to the selection of unsuccessful drug leads and subsequent clinical failure. It is evident that the limited understanding of how the brain works and the complexity of neurodegenerative processes, together with lack of good, predictive pre-clinical models, make drug development for CNS diseases particularly difficult.<\/p>\n

Um doktorsefni\u00f0<\/strong><\/p>\n

Natalia f\u00e6ddist \u00ed Su\u00f0ur-P\u00f3llandi \u00ed n\u00f3vember 1986. H\u00fan lag\u00f0i stund \u00e1 efnafr\u00e6\u00f0i vi\u00f0 T\u00e6knih\u00e1sk\u00f3lann \u00ed Rzesz\u00f3w og \u00fatskrifa\u00f0ist me\u00f0 MSc-gr\u00e1\u00f0u \u00ed efnaverkfr\u00e6\u00f0i, me\u00f0 s\u00e9rh\u00e6fingu \u00ed efnagreiningu \u00e1ri\u00f0 2010. MSc-verkefni hennar fjalla\u00f0i um einangrun og greiningu efnasambanda \u00far birkisveppum og hemjandi \u00e1hrif \u00feeirra \u00e1 krabbameinsfrumur. Natal\u00eda h\u00e9lt \u00e1fram a\u00f0 rannsaka n\u00e1tt\u00faruefni og h\u00f3f doktorsn\u00e1m vi\u00f0 H\u00e1sk\u00f3la \u00cdslands \u00e1ri\u00f0 2011 og vann fyrst me\u00f0 alkal\u00f3\u00ed\u00f0a \u00far \u00edslenskum j\u00f6fnum og hindrandi \u00e1hrif \u00feeirra \u00e1 aset\u00fdlk\u00f3l\u00ednesterasa og f\u00e6r\u00f0i sig svo inn \u00e1 svi\u00f0 nik\u00f3t\u00ednvi\u00f0taka og t\u00f6lvuhermiskimunar. Natal\u00eda vann hluta af verkefni s\u00ednu vi\u00f0 H\u00e1sk\u00f3lann \u00ed Sydney \u00ed \u00c1stral\u00edu og einnig vi\u00f0 Kaupmannahafnarh\u00e1sk\u00f3la \u00fear sem h\u00fan vann me\u00f0 nik\u00f3t\u00edn aset\u00fdlk\u00f3l\u00edn vi\u00f0taka og t\u00f6lvuhermia\u00f0fer\u00f0ir. Natalia hefur kennt t\u00f6luvert, b\u00e6\u00f0i lyfja- og efnafr\u00e6\u00f0i n\u00e1tt\u00faruefna og t\u00f6lvuhermil\u00edkanager\u00f0, samhli\u00f0a doktorsn\u00e1mi s\u00ednu vi\u00f0 Lyfjafr\u00e6\u00f0ideild.\u00a0<\/p>\n<\/div><\/div>","protected":false},"featured_media":1096,"template":"","meta":{"site-sidebar-layout":"default","site-content-layout":"","ast-site-content-layout":"default","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","ast-disable-related-posts":"","theme-transparent-header-meta":"","adv-header-id-meta":"","stick-header-meta":"","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"default","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"ast-content-background-meta":{"desktop":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"_phd_date_start":"2020-01-15T13:00:00+00:00","_phd_date_end":"2020-01-15T16:00:00+00:00","_phd_location":"A\u00f0albygging H\u00e1t\u00ed\u00f0asalur","_phd_admission":"A\u00f0gangur \u00f3keypis","_phd_thesis_title":"Leit a\u00f0 lyfjasprotum og \u00e1skoranir vi\u00f0 leit n\u00fdrra lyfja gegn Alzheimers og \u00f6\u00f0rum taugahr\u00f6rnunarsj\u00fakd\u00f3mum. 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