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Motoneuronerkrankungen

Familiäre ALS, SMA, HMN

Motor neuron diseases

Familial ALS, SMA and HMN

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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.

Summary

Motor neuron diseases (MND) are a group of neurodegenerative disorders which are present in clinical, prognostic and genetic diversity. The most common MND are amyotrophic lateral sclerosis (ALS), proximal spinal muscular atrophy (SMA) and various forms of hereditary and sporadic lower motor neuron syndromes including hereditary motor neuropathies (HMN). Familial and „sporadic“ forms of ALS and lower motor neuron syndromes are known. The essential pathogenic findings in MND have emerged from molecular biological examinations of the hereditary forms of MND. In ALS, one consistent neuropathological feature is intraneuronal protein inclusions which arise from TDP-43, FUS, SOD1 or ataxin-2 aggregations. TDP-43, FUS, SOD1 and ataxin-2 are multifunctional DNA/RNA-binding proteins which are involved in transcription regulation. SMA and HMN are associated with different genes whose gene products may also be involved in RNA processing. A disturbance in the regulation of RNA possibly represents an overlapping pathophysiological characteristic in MND. The elucidation of common pathways in the cascade of motor neuron degeneration is an essential point of departure for molecular genetically defined treatment strategies both in ALS and in hereditary and sporadic lower motor neuron syndromes.

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  1. Klinik für Neurologie - OE 7210, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, 30625, Hannover, Deutschland

    S. Petri

  2. Klinik für Neurologie, Charité-Univesitätsmedizin Berlin, Campus Mitte, Berlin, Deutschland

    T. Meyer

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Petri, S., Meyer, T. Motoneuronerkrankungen. Nervenarzt 82, 697–706 (2011). https://doi.org/10.1007/s00115-010-2967-y

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