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Erschienen in: Der Nervenarzt 6/2011

01.06.2011 | Leitthema

Motoneuronerkrankungen

Familiäre ALS, SMA, HMN

verfasst von: Prof. Dr. S. Petri, T. Meyer

Erschienen in: Der Nervenarzt | Ausgabe 6/2011

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Zusammenfassung

Motoneuronenerkrankungen (MNE) sind eine Gruppe neurodegenerativer Erkrankungen, die eine klinische, prognostische und genetische Diversität aufweisen. Die häufigsten MNE sind die amyotrophe Lateralsklerose (ALS), die proximale spinale Muskelatrophie (SMA) und hereditäre und sporadische Vorderhornerkrankungen einschließlich der hereditären motorischen Neuropathien (HMN). Für die ALS und für proximale und distale spinale Muskelatrophien sind familiäre und „sporadische“ Verlaufsformen bekannt. Die wesentlichen pathogenetischen Erkenntnisse der MNE sind durch molekularbiologische Untersuchungen der hereditären MNE-Formen entstanden. Ein übereinstimmendes neuropathologisches Merkmal bei der ALS sind intraneuronale Proteininklusionen, die durch Aggregationen von TDP-43, FUS, SOD1 oder Ataxin-2 entstehen. TDP-43, FUS und Ataxin-2 sind multifunktionale DNA/RNA-Bindungsproteine, die an der Transkriptionsregulation beteiligt sind. Die SMA und HMN sind mit verschiedenen Genen assoziiert, deren Genprodukte ebenfalls an der RNA-Prozessierung beteiligt sein können. Möglicherweise ist eine Störung der RNA-Regulation ein überlappendes pathophysiologisches Merkmal bei den MNE. Die Aufklärung übereinstimmender Abschnitte der neuronalen Schädigungskaskade ist ein wesentlicher Ansatz zur Entwicklung einer molekulargenetisch definierten Therapiestrategie sowohl bei der ALS als auch bei hereditären und sporadischen Vorderhornerkrankungen.
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Metadaten
Titel
Motoneuronerkrankungen
Familiäre ALS, SMA, HMN
verfasst von
Prof. Dr. S. Petri
T. Meyer
Publikationsdatum
01.06.2011
Verlag
Springer-Verlag
Erschienen in
Der Nervenarzt / Ausgabe 6/2011
Print ISSN: 0028-2804
Elektronische ISSN: 1433-0407
DOI
https://doi.org/10.1007/s00115-010-2967-y