Open AccessGem Depletion: Amyotrophic Lateral Sclerosis and Spinal Muscular Atrophy Crossover
Author(s) -
Cauchi Ruben J.
Publication year - 2014
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.12242
Subject(s) - amyotrophic lateral sclerosis , spinal muscular atrophy , medicine , neuroscience , atrophy , physical medicine and rehabilitation , pathology , psychology , disease
Summary The determining factor of spinal muscular atrophy ( SMA ), the most common motor neuron degenerative disease of childhood, is the survival motor neuron ( SMN ) protein. SMN and its Gemin associates form a complex that is indispensible for the biogenesis of small nuclear ribonucleoproteins (sn RNP s), which constitute the building blocks of spliceosomes. It is as yet unclear whether a decreased capacity of SMN in sn RNP assembly, and, hence, transcriptome abnormalities, account for the specific neuromuscular phenotype in SMA . Across metazoa, the SMN ‐Gemins complex concentrates in multiple nuclear gems that frequently neighbour or overlap Cajal bodies. The number of gems has long been known to be a faithful indicator of SMN levels, which are linked to SMA severity. Intriguingly, a flurry of recent studies have revealed that depletion of this nuclear structure is also a signature feature of amyotrophic lateral sclerosis ( ALS ), the most common adult‐onset motor neuron disease. This review discusses such a surprising crossover in addition to highlighting the most recent work on the intricate world of spliceosome building, which seems to be at the heart of motor neuron physiology and survival.