Listen folks, we’ve got something incredible here, really fantastic. We’re talking about the ubiquitin proteasome system, the UPS, it’s huge. It’s the system that decides which proteins to break down, and let me tell you, it’s a big deal in neurodegenerative diseases. We’ve got these major histocompatibility complex, MHC molecules, they’re doing an amazing job presenting peptides, and they’re not just doing that, they’re also playing a big role in the brain, in things like synapse numbers and axon regeneration. It’s something, but the mechanisms, they’re mostly unknown, believe me.

So, we took these human induced pluripotent stem cells, iPSCs, turned them into neural stem cells, and then into motor neurons. We’re talking about a developmental model that’s going to help us understand the proteasome in developing motor neurons. And we did a proteomic analysis, which is a very smart thing to do, on skin fibroblasts, iPSCs, neural stem cells, and motor neurons. And we found big differences, huge differences in the proteasome subunits during development.

The proteins in fibroblasts, they’re different from the ones in neural stem cells and motor neurons. We confirmed it with Western blot analysis, very reliable, very accurate. We saw that the β5i subunit, it’s lower in motor neurons than in fibroblasts, and the β5 is higher. It’s clear, the constitutive proteasome subunits, they’re upregulated in iPSCs and NSCs from fibroblasts. And the β5i, it’s higher in motor neurons than in NSCs, but overall, motor neurons, they’re more about the constitutive proteasome structure.

What does this mean? It means that the proteasome composition, it’s very important for motor neuron development and for understanding neurodevelopmental diseases. We’re going to investigate further, and it’s going to be great. Stay tuned, because this is just the beginning, and it’s going to be huge.