Amyotrophic lateral sclerosis: an update on recent genetic insights

作者：Iguchi Yohei; Katsuno Masahisa; Ikenaka Kensuke; Ishigaki Shinsuke; Sobue Gen^*

来源：Journal of Neurology, 2013, 260(11): 2917-2927.

DOI：10.1007/s00415-013-7112-y

• Amyotrophic lateral sclerosis
• Motor neuron disease
• Protein aggregation
• RNA metabolism

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease affecting both upper and lower motor neurons. The prognosis for ALS is extremely poor, but there is a limited course of treatment with only one approved medication. A most striking recent discovery is that TDP-43 is identified as a key molecule that is associated with both sporadic and familial forms of ALS. TDP-43 is not only a pathological hallmark, but also a genetic cause for ALS. Subsequently, a number of ALS-causative genes have been found. Above all, the RNA-binding protein, such as FUS, TAF15, EWSR1 and hnRNPA1, have structural and functional similarities to TDP-43, and physiological functions of some molecules, including VCP, UBQLN2, OPTN, FIG4 and SQSTM1, are involved in a protein degradation system. These discoveries provide valuable insight into the pathogenesis of ALS, and open doors for developing an effective disease-modifying therapy.

• 出版日期2013-11