Modeling of TDP-43 proteinopathy by chronic oxidative stress identifies rapamycin as beneficial in ALS patient-derived 2D and 3D iPSC models.

Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disorder characterized neuropathologically by TDP-43 proteinopathy with loss of TDP-43 nuclear splicing activity and formation of cytoplasmic TDP-43 aggregates. The lack of suitable experimental models of TDP-43 proteinopathy has hampered the discovery of effective therapies. We already showed that chronic and mild oxidative insult by sodium arsenite (ARS) triggered TDP-43 cytoplasmic aggregation and stress granules (SGs) formation in ALS patient-derived fibroblasts and motor neurons differentiated from induced pluripotent stem cells (iPSC-MNs).

NEK1 haploinsufficiency worsens DNA damage, but not defective ciliogenesis, in C9ORF72 patient-derived iPSC-motoneurons.

The hexanucleotide G4C2 repeat expansion (HRE) in C9ORF72 gene is the major cause of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), leading to both loss- and gain-of-function pathomechanisms. The wide clinical heterogeneity among C9ORF72 patients suggests potential modifying genetic and epigenetic factors. Notably, C9ORF72 HRE often co-occurs with other rare variants in ALS/FTD-associated genes, such as NEK1, which encodes for a kinase involved in multiple cell pathways, including DNA damage response and ciliogenesis.

The duration discrimination respiratory task: A new test to measure respiratory interoceptive accuracy.

Interoception, which refers to the perception of body's internal state, is implicated in emotional processes and psychopathological disorders. Over the last decades, different tools have been developed to measure interoceptive accuracy, or the ability to accurately perceive physiological signals. Most of these tools have focused on cardiac interoception, but respiratory interoception has been less investigated due to the more complex and less portable equipment required.

Human motor neurons derived from induced pluripotent stem cells are susceptible to SARS-CoV-2 infection.

Introduction: COVID-19 typically causes Q7 respiratory disorders, but a high proportion of patients also reports neurological and neuromuscular symptoms during and after SARSCoV-2 infection. Despite a number of studies documenting SARS-CoV-2 infection of various neuronal cell populations, the impact of SARS-CoV-2 exposure on motor neuronal cells specifically has not been investigated so far.

Methods: Thus, by using human iPSC-derived motor neurons (iPSC-MNs) we assessed: (i) the expression of SARS-CoV-2 main receptors; (ii) iPSC-MN infectability by SARS-CoV-2; and (iii) the effect of SARS-CoV-2 exposure on iPSC-MN transcriptome.

Analysis of normal repeat length as possible disease modifier in amyotrophic lateral sclerosis.

The hexanucleotide repeat (HR) expansion is the main genetic cause of amyotrophic lateral sclerosis (ALS), with expansion size from 30 to >4000 units. Normal HR length is polymorphic (2-23 repeats) with alleles >8 units showing a low frequency in the general population. This study aimed to investigate if the normal HR length influences gene expression and acts as disease modifier in ALS patients negative for mutation (ALS-C9Neg).