Details

Autor(en) / Beteiligte

• Aquilina, Beppe
• Cauchi, Ruben J.

Titel

Modelling motor neuron disease in fruit flies: Lessons from spinal muscular atrophy

Ist Teil von

• Journal of neuroscience methods, 2018-12, Vol.310, p.3-11

Ort / Verlag

Netherlands: Elsevier B.V

Erscheinungsjahr

2018

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• •Genetic factors play a major role in MND pathogenesis and progression.•SMA, caused by mutations in the SMN1 gene, leads to muscle weakness and paralysis.•Fruit fly models of SMA have a phenotypic overlap with patients and mammalian models.•Discovery of genetic and chemical modifiers can lead to complementary SMA therapies.•SMA fly models pave the way for MND modelling in Drosophila. Motor neuron disease (MND) is characterised by muscle weakness and paralysis downstream of motor neuron degeneration. Genetic factors play a major role in disease pathogenesis and progression. This is best underscored by spinal muscular atrophy (SMA), the most common MND affecting children. Although SMA is caused by homozygous mutations in the survival motor neuron 1 (SMN1) gene, partial compensation by the paralogous SMN2 gene and/or genetic modifiers influence age of onset and disease severity. SMA is also the first MND that is treatable thanks to the recent development of a molecular-based therapy. This key milestone was possible following an intense research campaign in which animal models had a starring role. In this review, we specifically focus on the fruit fly Drosophila melanogaster and highlight its sterling contributions aimed at furthering our understanding of SMA pathogenesis. Methods of gene disruption utilised to generate SMA fly models are discussed and ways through which neuromuscular defects have been characterised are elaborated on. A phenotypic overlap with patients and mammalian models, allowed the use of SMA fly models to identify genetic modifiers, hence spurring investigators to discover pathways that are perturbed in disease. Targeting these can potentially lead to complimentary therapies for SMA. The same output is expected from the use of SMA fly models to identify therapeutic compounds that have an ameliorative effect. We believe that lessons gained from SMA will allow researchers to eagerly exploit Drosophila to confirm novel genes linked to MND, reveal disease mechanisms and ultimately identify therapeutics.