I heard about Giovanni in the news a couple of weeks ago..

And I received an email today from Michael Guglielmo, the father of Baby Giovanni who was just diagnosed with NEMO yesterday.
We talked on the phone, he’s looking for information about NEMO, he said he’s had a hard time finding information about the disease…
Here is Dr. Orange’s latest NEMO article:

IL-1-induced NF-kappa B1 activation is NEMO-dependent but does not require IKKbeta. Activation of NF-B by the pro-inflammatory cytokines TNF and IL-1 requires the IB kinase (IKK) complex that contains two kinases named IKKa and IKKss and a critical regulatory subunit named NEMO. Although we previously demonstrated that NEMO associates with both IKKs, genetic studies reveal that only its interaction with IKKss is required for TNF-induced NF-B activation. To determine whether NEMO and IKKa can form a functional IKK complex capable of activating the classical NF-B pathway in the absence of IKKss we utilized a panel of mouse embryonic fibroblasts (MEFs) lacking each of the IKK complex subunits. This confirmed that TNF-induced IBa degradation absolutely requires NEMO and IKKss. In contrast we consistently observed intact IBa degradation and NF-B activation in response to IL-1 in two separate cell lines lacking IKKss. Furthermore, exogenously expressed, catalytically inactive IKKss blocked TNF- but not IL-1-induced IBa degradation in wild-type MEFs and reconstitution of IKKa/ss double knock-out cells with IKKa rescued IL-1- but not TNF-induced NF-B activation. Finally we show that incubation of IKKss-deficient MEFs with a cell-permeable peptide that blocks the interaction of NEMO with the IKKs inhibits IL-1-induced NF-B activation. Our results therefore demonstrate that NEMO and IKKa can form a functional IKK complex that activates the classical NF-B pathway in response to IL-1 but not TNF. These findings further suggest NEMO differentially regulates the fidelity of the IKK subunits activated by distinct upstream signaling pathways.

I didnt understand either….
Article link via Pub Med
Visit Giovanni’s website.