TDP-43 mislocalization and aggregation are implicated in the pathogenesis of ALS and FTLD-U. Valosin containing protein (VCP) mutations also lead to TDP-43 deposition, resulting in Inclusion Body Myopathy, Paget disease, and Frontotemporal Dementia (IBMPFD). In this issue of Neuron, Johnson et al. used whole-exome capture to identify VCP mutations in familial ALS. This extends the VCP phenotype...

A patient with a progressive lower motor neuron syndrome and neurophysiological evidence of motor axon loss, multifocal proximal motor nerve conduction block, and high titres of anti-ganglioside GM1 antibodies. Neuropathological findings included a predominantly proximal motor radiculoneuropathy with multifocal IgG and IgM deposits on nerve fibres associated with a loss of spinal motor neurons....

We sought genetic evidence for the involvement of neuronal vascular endothelial growth factor (VEGF) in amyotrophic lateral sclerosis (ALS). Mice expressing human ALS mutant superoxide dismutase-1 (SOD1) were crossed with mice that overexpress VEGF in neurons (VEGF+/+). We report that SOD1(G93A)/VEGF+/+ double-transgenic mice show delayed motor neuron loss, delayed motor impairment, and prolong...

Abundant evidence indicates that mitochondrial dysfunction and Ca(2+) dysregulation contribute to the muscle denervation and motor neuron death that occur in mouse models of familial amyotrophic lateral sclerosis (fALS). This perspective considers measurements of mitochondrial function and Ca(2+) handling made in both motor neuron somata and motor nerve terminals of SOD1-G93A mice at different ...