ALS

…mitochondrial biology and a reported ALS case study involving an antisense oligonucleotide treatment. Giuliana Galati interviews University of Padua physicist Francesco Recchia about nuclear phenomenology. The episode links these discussions to the underlying research papers and distinguishes a clinical case report from established treatment evidence.

…amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) is the depletion of RNA-binding protein TDP-43 from the nucleus of neurons in the brain and spinal cord. A major function of TDP-43 is as a repressor of cryptic exon inclusion during RNA splicing. By re-analyzing RNA-sequencing datasets from human FTD/ALS brains, we discovered dozens of novel cryptic splicing events in important neuronal genes. Single nucleotide polymorphisms in UNC13A are among the strongest hits associated with FTD and ALS in human genome-wi

ALS is the most common motor neuron disease in humans, whereby upper and lower motor neurons degenerate. A major hypothesis underlying the mechanistic origin of neurodegeneration in ALS postulates that cortical hyperexcitability facilitates cell death. Previous research has identified the G4C2 hexanucleotide repeat expansion in the C9orf72 gene as the most common genetic cause of ALS; however, little is known about the contribution of the C9orf72 gene to neuronal excitability and synaptic dysfunction in the primary motor cortex. Thus, using C9orf72 knockout loss-of-function (C9-KO LOF) and gai

…well understood and preventable in animals. Its aberrant activation by mutation of the pro-survival gene Nmnat2 directly causes axonopathy in mice with severity ranging from mild polyneuropathy to perinatal lethality. Rare biallelic mutations in the homologous human gene cause related phenotypes in patients. NMNAT2 is a negative regulator of the prodegenerative NADase SARM1. Constitutive activation of SARM1 is cytotoxi