Impact of Neurons on Patient-Derived Cardiomyocytes Using Organ-On-A-Chip and iPSC Biotechnologies.

In the heart, cardiac function is regulated by the autonomic nervous system (ANS) that extends through the myocardium and establishes junctions at the sinus node and ventricular levels. Thus, an increase or decrease in neuronal activity acutely affects myocardial function and chronically affects its structure through remodeling processes. The neuro-cardiac junction (NCJ), which is the major structure of this system, is poorly understood and only a few cell models allow us to study it.

Genuine selective caspase-2 inhibition with new irreversible small peptidomimetics.

Caspase-2 (Casp2) is a promising therapeutic target in several human diseases, including nonalcoholic steatohepatitis (NASH) and Alzheimer's disease (AD). However, the design of an active-site-directed inhibitor selective to individual caspase family members is challenging because caspases have extremely similar active sites. Here we present new peptidomimetics derived from the VDVAD pentapeptide structure, harboring non-natural modifications at the P2 position and an irreversible warhead.

Dysregulated Neurotransmission induces Trans-synaptic degeneration in reconstructed Neuronal Networks.

Increasing evidence suggests that pathological hallmarks of chronic degenerative syndromes progressively spread among interconnected brain areas in a disease-specific stereotyped pattern. Functional brain imaging from patients affected by various neurological syndromes such as traumatic brain injury and stroke indicates that the progression of such diseases follows functional connections, rather than simply spreading to structurally adjacent areas. Indeed, initial damage to a given brain area was shown to disrupt the communication in related brain networks.

Nicotinamide riboside, a form of vitamin B, protects against excitotoxicity-induced axonal degeneration.

NAD depletion is a common phenomenon in neurodegenerative pathologies. Excitotoxicity occurs in multiple neurologic disorders and NAD was shown to prevent neuronal degeneration in this process through mechanisms that remained to be determined. The activity of nicotinamide riboside (NR) in neuroprotective models and the recent description of extracellular conversion of NAD to NR prompted us to probe the effects of NAD and NR in protection against excitotoxicity.

Acute amnestic encephalopathy in amyloid-β oligomer-injected mice is due to their widespread diffusion in vivo.

Amyloid-β (Aβ) oligomers are the suspected culprit as initiators of Alzheimer's disease (AD). However, their diffusion in the brain remains unknown. Here, we studied Aβ oligomers' dissemination and evaluated their in vivo toxicity.