First we report that loneliness is related to the rate of motor decline derived from objective motor performances tested annually for up to 12 years.
In addition to ALS animal models, motor neurons derived from human-derived induced pluripotent stem cells (iPSCs) could be used to explore the role of DNA damage in ALS pathogenesis, particularly whether motor neurons harboring ALS-linked FUS mutations are more susceptible to DNA-damaging agents.
Although the motor phenotype derived from corticospinal tract and peripheral motor nerve degeneration is a hallmark of ALS, there is increasing evidence that ALS could be a multisystem disorder affecting also the somatosensory cortex [ 6], autonomic system [ 7], spinocerebellar tracts [ 8], and serotoninergic neurons [ 9].
VAPB is expressed diffusely in the cytoplasm of motor neurons derived from ALS8-iPSCs similar to control motor neurons (Fig. 3G and H).
Not only did motor neurons die before other types of neurons, but motor neurons derived from patients with severe SMA died very quickly in comparison to those made from patients with a milder form of the disease.
Motor skills were assessed by an obstacle course including 5 motor skills, derived from the Zurich Neuromotor Assessment test.
Motoric block was quantified using an established motor score derived from the Bromage score and adapted to rats [ 33].
We therefore analysed the Δ ψm of embryonic motor neurons derived from WT and Sod1 +/− littermates and found that Sod1 +/− motor neurons also have elevated Δ ψm (Fig. 8).
The continuous firing of motor units in the PFMs is related to an appropriate excitatory set-up of their motor neurons derived from suprasegmental and segmental inputs [ 20].
Compatible with this idea, mutant VAPB inclusions do not occur in motor neurons of low-expressing mutant VAPB transgenic mice (line VM2), and are absent in motor neurons derived from induced pluripotent stem cells of ALS8 patients [ 57].
Similar to the observations in the iPSC lines from which they are differentiated, the motor neurons derived from the FUS-P525L mutant line showed significant cytoplasmic FUS accumulation compared to WT FUS motor neurons, while the FUS-R521H motor neurons showed only moderate cytoplasmic accumulation (Fig. 5f).
