Serena Stanga, Université catholique de Louvain - Brussels

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Data dell'evento: 17/05/2018
seminars_2018

INN Open Neuroscience Forum

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Friday, 18th May – h. 12:00
Seminars Room, NICO

Serena Stanga, PhD
Alzheimer Research group/CEMO, Institute of Neuroscience (IoNS)
Université catholique de Louvain (UCL) - Brussels (Belgium)

APP and Presenilins: biological function and role in neurodegenerative and neuromuscular diseases

The major role of the Amyloid Precursor Protein (APP) in the onset and progression of Alzheimer's disease (AD) has been revealed almost three decades ago by the combination of genetic and biochemical approaches, leading to the amyloid cascade hypothesis. Similarly to APP, Presenilins (PSs), the catalytic core of the multiprotein enzymatic complex (β-secretase) generating the beta-amyloid peptide (Aβ), are mainly studied for their role in the ultimate step of APP amyloidogenic processing.

Apart from generating Aβ, the major constituent of senile plaques that are typical AD lesions directly related to AD onset and progression, the pivotal physiological role of APP and how PSs could impact it remains scarcely known or controversial. A leading hypothesis suggests that APP function relies on the transcriptional regulation that APP exerts on a set of target genes, the so-called APP target genes.

In this context, we contributed to a more comprehensive picture of APP regulatory network and physiological function by showing that APP-dependent regulation of the Glial cell line-Derived Neurotrophic Factor (GDNF) drives the process of neuronal and muscular maturation involved in neuromuscular junctions (NMJs) formation (Stanga et al. FASEB J 2016). APP-dependent GDNF transcription appears as critical for the muscular phenotype observed in APP null transgenic mice (APP-/-).

Moreover, in a non-biased transcriptome analysis, we observed that GDNF transcription is strongly reduced in PSs deficient mouse embryonic fibroblasts (MEFs); interestingly, Presenilin 2 (PS2) appears to be predominant in this process.
It is therefore of particular significance to understand the molecular mechanisms recruited by APP/PS2 to control the expression of the GDNF, a neurotrophic factor fundamental for both central nervous system (CNS) and peripheral nervous system (PNS) neuron survival and, importantly, altered in AD and amyotrophic lateral sclerosis (ALS).

Host: Alessandro Vercelli

Agenda

25 novembre 2021

Sportello LESIONI SPINALI

Mandateci le vostre domande

Premesso che al NICO ci occupiamo di ricerca di base (e non abbiamo quindi pazienti in cura), crediamo sia compito di noi ricercatori dare risposte chiare e soprattutto scientificamente corrette a chi incorre in notizie parzialmente false, scorrette o addirittura in vere e proprie bufale.
Il caso Stamina ci ha insegnato a essere vigili: un piccolo soffio di vento, se “seminato” in un terreno fertile, può infatti scatenare una pericolosa tempesta.

Da qui la volontà di creare questo sportello, uno spazio dedicato alle vostre domande e ai vostri dubbi. Un progetto nato in sinergia con il Coordinamento Para-Tetraplegici del Piemonte, con cui siamo in contatto da molto tempo, e con il Prof. Diego Garbossa, Primario di Neurochirurgia di Città della Salute e della Scienza di Torino, con cui abbiamo creato un team che riunisce ricerca base e neurochirurgia.

Inviate le vostre domande e le leggete alcune delle nostre risposte

31 agosto 2020