Ricerc@Sapienza

In adult mammals, neural stem cells (NSCs) reside in specialized niches at the level of selected CNS regions, such as the subventricular zone (SVZ). The signalling pathways that regulate NSCs proliferation and differentiation remain poorly understood. The early growth response gene 1 (Egr-1) is an important transcription factor, widely studied in the adult mammalian brain, mediating the activation of target genes by a variety of extracellular stimuli.

Mutations of Fused in sarcoma (FUS), a ribonucleoprotein involved in RNA metabolism, have been found associated with both familial and sporadic cases of amyotrophic lateral sclerosis (ALS). Notably, besides mutations in the coding sequence, also mutations into the 3′ untranslated region, leading to increased levels of the wild-type protein, have been associated with neuronal death and ALS pathology, in ALS models and patients.

The immunohistochemical evidence provided by the present authors about the persistence of latent naturai brain proliferative potentially in adult vertebrate brain and its response to cyclic seasonal environmental fluctuations (temperature, photoperiod) has been reviewed. These stimuli elicit an otherwise hidden mitotic activity thanks to stem cells still present especially in less high vertebrates like Triturus carni/ex, Rana bergeri, Podarcis sicula.

Exosomes, small vescicles with a lipid bilayer, are released from many cell types and are part of the cell secretrome that can play a role in intercellular communication. They originate from cytoplasmic multivescicular bodies, fuse with the plasma membrane and release their content of lipids, proteins and RNAs in the extracellular space or in target cells. A growing body of evidence suggests that exosomes contribute to many aspects of healthy and pathological cells, and they may influence the homeostasis of target cells.

Numb is an intracellular protein with multiple functions. The two prevalent isoforms, Numb p66 and Numb p72, are regulators of differentiation and proliferation in neuronal development. Additionally, Numb functions as cell fate determinant of stem cells and cancer stem cells and its abnormal expression has been described in several types of cancer. Involvement of deregulated Numb expression has been described in the malignant childhood brain tumor medulloblastoma, while Numb isoforms in these tumors and in cancer stem-like cells derived from them, have not been studied to date.