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Neuronale Zeroidlipofuszinosen (NCL) im Tiermodell

NCL in animal models

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Zusammenfassung

Neuronale Zeroidlipofuszinosen (NCL) sind schwer verlaufende und zum vorzeitigen Tod führende neurodegenerative Erkrankungen. Sie gehören zu der Gruppe der lysosomalen Speichererkrankungen. Epileptische Anfälle, Demenz und motorische Defizite sind häufige Symptome, die vor dem gänzlichen Persönlichkeitsabbau und Tod anzutreffen sind. Man unterscheidet zurzeit 10 Unterformen; bei 8 Varianten ist die genetische Grundlage bekannt. Bei den involvierten Proteinen handelt es sich um zytoplasmatische oder Membranproteine, deren Funktion jedoch in den meisten Fällen noch unklar ist. Die Erforschung der Pathologie und Pathophysiologie der NCL ist in hohem Maße von Tiermodellen abhängig, wobei Mausmodelle, die es für alle Unterformen mit bekanntem Gendefekt gibt, eine herausragende Rolle spielen. Leider ist der retinale Phänotyp bei einigen Mausmodellen nicht so ausgeprägt wie beim Menschen, was die Beurteilung eines positiven Therapieeffekts erschwert. Aufgrund des Schweregrads der NCL werden schon heute lediglich im Mausmodell untersuchte Therapiestrategien beim Menschen angewendet.

Abstract

Neuronal ceroid lipofuscinoses (NCL) are severe neurodegenerative diseases leading to early death. They belong to the group of lysosomal storage diseases. Epileptic seizures, dementia and motor deficits are frequent symptoms which are to be found prior to a total dismantling of personality and death. At present 10 subtypes of NCL can be distinguished from which the genetic defect is known in eight. The encoded proteins are soluble or membrane proteins whose function is still unclear in most cases. The investigation of the pathology and pathophysiology of NCL is highly dependent on animal models. Mouse models existing for all forms with a known genetic defect play a prominent role. Unfortunately, the retinal phenotype of some mouse models is milder than in humans rendering the appreciation of a positive therapeutic effect more difficult. Because of the severity of NCL, therapy strategies only established in a mouse model will be transferred to humans very quickly.

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  1. Arbeitsbereich Strabologie/Neuroophthalmologie, Augenklinik, Charité – Universitätsmedizin Berlin, Campus Virchow-Klinikum, Augustenburger Platz 1, 13353, Berlin, Deutschland

    K. Rüther

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Rüther, K. Neuronale Zeroidlipofuszinosen (NCL) im Tiermodell. Ophthalmologe 107, 621–627 (2010). https://doi.org/10.1007/s00347-009-2108-9

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