Abstrakt

Choroba Alzheimera (AD, Alzheimer’s disease) opisywana jako przewlekłe i nieodwracalne schorzenie neurodegeneracyjne pozostaje najczęstszą przyczyną demencji. Ze względu na obserwowane od dłuższego czasu zjawisko starzenia się populacji, nieuleczalność AD stała się narastającym problem medycyny XXI w. Obecne metody leczenia mają wyłącznie charakter objawowy, zapewniają minimalne, czasowe usprawnienie funkcji poznawczych pacjentów. W pracy przedstawiono najnowsze kierunki poszukiwań skutecznej farmakoterapii zdolnej do zapobieżenia lub zahamowania progresji AD. Ze względu na to, iż nie jest znana dokładna patogeneza choroby Alzheimera główne strategie terapeutyczne opierają się jedynie na hipotezach: kaskady amyloidowej, białka tau, stresu oksydacyjnego, neurozapalenia oraz tych związanych z dysfunkcją układu cholinergicznego, jak również glutaminianergicznego. Większość związków obecnie testowanych w badaniach klinicznych nakierowana jest na patologiczny amyloid β (Aβ), będący narzędziem sprawczym neurodegeneracji, według opisywanej dotychczas najszerzej teorii kaskady amyloidowej. Z toksycznym Aβ próbuje się walczyć za pośrednictwem: immunoterapii (szczepionki, przeciwciała monoklonalne), związków hamujących jego powstanie: inhibitorów/modulatorów γ-sekretazy i inhibitorów β-sekretazy. Immunoterapię próbuje się wykorzystać również do nasilenia klirensu hiperfosforylowanego białka tau, którego obecność jest nieodzowną cechą choroby Alzheimera. Oprócz przedstawicieli immunoterapii, przedmiotem prac badawczych stały się również związki o działaniu przeciwzapalnym, metabolicznym i neuroprotekcyjnym. W fazę badań klinicznych zostały wprowadzone ponadto związki działające objawowo, które wyrównując deficyty cholinergiczne, noradrenergiczne i glutaminianergiczne poprawiają funkcje poznawcze.

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