Nuclear Factor \u3baB-Dependent Neurite Remodeling Is Mediated by Notch Pathway

In this study, we evaluated whether a cross talk between nuclear factor \u3baB (NF-\u3baB) and Notch may take place and contribute to regulate cell morphology and/or neuronal network in primary cortical neurons. We found that lack of p50, either induced acutely by inhibiting p50 nuclear translocation or genetically in p50(-/-) mice, results in cortical neurons characterized by reduced neurite branching, loss of varicosities, and Notch1 signaling hyperactivation. The neuronal morphological effects found in p50(-/-) cortical cells were reversed after treatment with the \u3b3-secretase inhibitor DAPT (N-[N-(3,5-difluorophenacetyl)-1-alanyl 1]-S-phenylglycine t-butyl ester) or Notch RNA interference. Together, these data suggested that morphological abnormalities in p50(-/-) cortical neurons were dependent on Notch pathway hyperactivation, with Notch ligand Jagged1 being a major player in mediating such effect. In this line, we demonstrated that the p50 subunit acts as transcriptional repressor of Jagged1. We also found altered distribution of Notch1 and Jagged1 immunoreactivity in the cortex of p50(-/-) mice compared with wild-type littermates at postnatal day 1. These data suggest the relevance of future studies on the role of Notch/NF-\u3baB cross talk in regulating cortex structural plasticity in physiological and pathological conditions

Conformationally altered p53: a putative predictive marker from mci to alzheimer’s disease?

Background: When evaluating the intermediate state between normal aging and established AD, known as mild cognitive impairment (MCI), not all MCI patients progress to AD and hence there is a need of a reliable prediction tool able to identify which patients with MCI will progress to AD. Recently a role for conformationally altered p53 as a novel candidate biomarker for early onset AD has been described. Aim: To investigate the usefulness of this method especially for younger patients, thus supporting its putative application for subjects with MCI and earlier in the clinical course of AD. Methods: We used a flow-cytometric approach to investigate the different expression of conformationally altered p53 among MCI, AD and non-AD subjects on peripheral blood cells. Results: We found that peripheral blood cells from MCI specifically expressed increased levels of unfolded p53 compared to age-matched controls. We found that the expression of conformationally altered p53 is age dependent. For our preliminary data analysis we have arbitrarily worked out the related cut-points by linear regression, taking as reference linear fit of controls, thus dividing the subjects in specific age interval segments. Young (< 70 years) MCI patients show levels of conformationally altered p53 comparable to those measured in AD patients, but significantly different from subjects of control group. Conclusions: The highest levels of conformationally altered p53 have been observed in amnestic MCI patients, which represent an early stage of AD, thus supporting the promise of this protein measurement to accurately identify this at-risk group

Hearing loss and cognitive decline in older adults: Questions and answers

The association between hearing impairment, the diagnosis of dementia, and the role of sensory therapy has been proposed for some time, but further research is needed. Current understanding of this association requires the commitment of those experts who can integrate experience and research from several fields to be able to understand the link from hearing to dementia. A workshop whose panelists included experts from many areas, ranging from ear, nose and throat (ENT) to dementia\u2019s specialists, was promoted and organized by the Giovanni Lorenzini Medical Science Foundation (Milan, Italy; Houston, TX, USA) to increase the awareness of the relationship between hearing loss and dementia, and included questions and comments following a presentation from the clinical researcher, Frank Lin, who has been evaluating the relationship between hearing loss and cognitive decline since 2009