Several factors may affect cell survival in the acute phase of cerebral infarction, including limited blood supply, hypoxia, trophic factor deficiency, oxidative stress, inflammatory response, and others [ 169].
IGF-I has trophic effects on intestinal epithelia, so IGF-1 deficiency could cause intestinal barrier dysfunction.
Robust mTOR activation in the context of OXPHOS deficiency is counterintuitive because mTOR integrates trophic factor and nutrient availability signals to regulate cell growth and proliferation [ 9], and poisoning of mitochondrial energy production inhibits mTOR [ 10].
Lack of this trophic factor will negatively impact MSSNs.
In our casuistry, 5 7 days after injury, all patients had evident signs of corneal suffering with epithelial instability and inflammation that was caused by trophic damage on the cornea and conjunctiva, despite limited limbal deficiency.
This supports our hypothesis that the specific neurolysosomal pathology in human pSap deficiency may be closely related to the absence of pSap´s trophic function.
In view of global IL7-unresponsiveness of Gfi1−/− cells affecting trophic, proliferative, and differentiation-inducing cellular responses, we reasoned that Gfi1-deficiency affected early IL7Rα signalling events such as activation of the JAK/STAT pathway.
It is therefore possible that the interruption of an IFNγ-dependent feed-forward trophic mechanism (27), sustaining frataxin levels, might contribute to the exquisite sensitivity of DRG to frataxin deficiency.
However, in the peripheral and central neurons, the consequences of pSap deficiency seem to be determined by the unique sensitivity of the neurons to the lack of a trophic effect of secreted unprocessed pSap.
In this disease, there is not a single deficiency of tears but rather an imbalance with the production of harmful substance and an increased need for trophic factors.
