[Motor neuron diseases]. / Motoneuronerkrankungen. Familiäre ALS, SMA, HMN Familial ALS, SMA and HMN.

ABSTRACT

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.