Age-dependent degeneration of an identified adult leg motor neuron in a SOD1 model of ALS.

Mutations in superoxide dismutase 1 (SOD1) cause familial amyotrophic lateral sclerosis (ALS) in humans. ALS is a neurodegenerative disease characterized by progressive motor neuron loss leading to paralysis and inevitable death in affected individuals. Using a gene replacement strategy to introduce disease mutations into the orthologous () gene, here, we characterize changes at the neuromuscular junction using longer-lived mutant adults.

Circuit Dysfunction in Model First Detected in Sensory Feedback Prior to Motor Neuron Degeneration Is Alleviated by BMP Signaling.

Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease for which the origin and underlying cellular defects are not fully understood. Although motor neuron degeneration is the signature feature of ALS, it is not clear whether motor neurons or other cells of the motor circuit are the site of disease initiation. To better understand the contribution of multiple cell types in ALS, we made use of a knock-in model, in which all cells harbor the disease allele.

Meta-analysis of Genetic Modifiers Reveals Candidate Dysregulated Pathways in Amyotrophic Lateral Sclerosis.

Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease that has significant overlap with frontotemporal dementia (FTD). Mutations in specific genes have been identified that can cause and/or predispose patients to ALS. However, the clinical variability seen in ALS patients suggests that additional genes impact pathology, susceptibility, severity, and/or progression of the disease.

Give me a SINE: how Selective Inhibitors of Nuclear Export modulate autophagy and aging.

Autophagy is a cellular recycling process leading to lysosomal degradation of damaged macromolecules, which can protect cells against aging. The transcription factor EB (TFEB), a major transcriptional regulator of genes involved in autophagy and lysosomal function, is emerging as an attractive target for pharmacological modulation. Recently, we demonstrated that inhibiting the function of nuclear export protein exportin 1 (XPO1 or CRM1) with RNAi or with selective inhibitors of nuclear export (SINE) results in the nuclear enrichment of TFEB and enhancement of autophagy in model organisms and human cells.