Etude des gènes régulés par le PACAP au cours de la différenciation des cellules de phéochromocytome : rôle du nuclear factor kappa B, du tumor necrosis factor alpha et de la sélénoprotéine T

ROUEN-BU Sciences (764512102) / SudocROUEN-BU Sciences Madrillet (765752101) / SudocSudocFranceF

The Neuroprotective Role of Protein Quality Control in Halting the Development of Alpha-Synuclein Pathology

Synucleinopathies are a family of neurodegenerative disorders that comprises Parkinson’s disease, dementia with Lewy bodies, and multiple system atrophy. Each of these disorders is characterized by devastating motor, cognitive, and autonomic consequences. Current treatments for synucleinopathies are not curative and are limited to improvement of quality of life for affected individuals. Although the underlying causes of these diseases are unknown, a shared pathological hallmark is the presence of proteinaceous inclusions containing the α-synuclein (α-syn) protein in brain tissue. In the past few years, it has been proposed that these inclusions arise from the self-templated, prion-like spreading of misfolded and aggregated forms of α-syn throughout the brain, leading to neuronal dysfunction and death. In this review, we describe how impaired protein homeostasis is a prominent factor in the α-syn aggregation cascade, with alterations in protein quality control (PQC) pathways observed in the brains of patients. We discuss how PQC modulates α-syn accumulation, misfolding and aggregation primarily through chaperoning activity, proteasomal degradation, and lysosome-mediated degradation. Finally, we provide an overview of experimental data indicating that targeting PQC pathways is a promising avenue to explore in the design of novel neuroprotective approaches that could impede the spreading of α-syn pathology and thus provide a curative treatment for synucleinopathies

Pituitary Adenylate Cyclase-activating Polypeptide (PACAP) Promotes Both Survival and Neuritogenesis in PC12 Cells through Activation of Nuclear Factor κB (NF-κB) Pathway

International audienceThe pituitary adenylate cyclase-activating polypeptide (PACAP) is a trophic factor that promotes neuronal survival and neurite outgrowth. However, the signaling pathways and the transcriptional mechanisms involved are not completely elucidated. Our previous studies aimed at characterizing the transcriptome of PACAP-differentiated PC12 cells revealed an increase in the expression of nuclear factor κB2 (NF-κB2) gene coding for p100/p52 subunit of NF-κB transcription factor. Here, we examined the role of the NF-κB pathway in neuronal differentiation promoted by PACAP. We first showed that PACAP-driven survival and neuritic extension in PC12 cells are inhibited following NF-κB pathway blockade. PACAP stimulated both c-Rel and p52 NF-κB subunit gene expression and nuclear translocation, whereas c-Rel down-regulation inhibited cell survival and neuritogenesis elicited by the neuropeptide. PACAP-induced c-Rel nuclear translocation was inhibited by ERK1/2 and Ca2+ blockers. Furthermore, the neuropeptide stimulated NF-κB p100 subunit processing into p52, indicative of activation of the NF-κB alternative pathway. Taken together, our data show that PACAP promotes both survival and neuritogenesis in PC12 cells by activating NF-κB pathway, most likely via classical and alternative signaling cascades involving ERK1/2 kinases, Ca2+, and c-Rel/p52 dimers

AMPK Activation of PGC-1α/NRF-1-Dependent SELENOT Gene Transcription Promotes PACAP-Induced Neuroendocrine Cell Differentiation Through Tolerance to Oxidative Stress

International audienc

AMPK Activation of PGC-1α/NRF-1-Dependent SELENOT Gene Transcription Promotes PACAP-Induced Neuroendocrine Cell Differentiation Through Tolerance to Oxidative Stress

International audienc

The PACAP-regulated gene selenoprotein T is highly induced in nervous, endocrine, and metabolic tissues during ontogenetic and regenerative processes.

International audienceSelenoproteins contain the essential trace element selenium whose deficiency leads to major disorders including cancer, male reproductive system failure, or autoimmune thyroid disease. Up to now, 25 selenoprotein-encoding genes were identified in mammals, but the spatiotemporal distribution, regulation, and function of some of these selenium-containing proteins remain poorly documented. Here, we found that selenoprotein T (SelT), a new thioredoxin-like protein, is regulated by the trophic neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) in differentiating but not mature adrenomedullary cells. In fact, our analysis revealed that, in rat, SelT is highly expressed in most embryonic structures, and then its levels decreased progressively as these organs develop, to vanish in most adult tissues. In the brain, SelT was abundantly expressed in neural progenitors in various regions such as the cortex and cerebellum but was undetectable in adult nervous cells except rostral migratory-stream astrocytes and Bergmann cells. In contrast, SelT expression was maintained in several adult endocrine tissues such as pituitary, thyroid, or testis. In the pituitary gland, SelT was found in secretory cells of the anterior lobe, whereas in the testis, the selenoprotein was present only in spermatogenic and Leydig cells. Finally, we found that SelT expression is strongly stimulated in liver cells during the regenerative process that occurs after partial hepatectomy. Taken together, these data show that SelT induction is associated with ontogenesis, tissue maturation, and regenerative mechanisms, indicating that this PACAP-regulated selenoprotein may play a crucial role in cell growth and activity in nervous, endocrine, and metabolic tissues

L'ordinaire des sciences et techniques. Cultures populaires, cultures informelles (6)

International audienceLa présente édition de la Lucarne matérialise la poursuite d’un travail engagé depuis 2013. Comme pour la précédente livraison, il a été réalisé dans le cadre d’un atelier collaboratif d’histoire socioculturelle. L’atelier lui-même est animé par un collectif formé des enseignant∙e∙s et auditeur∙rice∙s des formations du CNAM dédiées à la médiation socioculturelle des sciences et techniques. Certificat de compétences, Licence professionnelle ou Magister s’attèlent ainsi à la réflexion, à la conception et à la réalisation de dispositifs pour la médiation des sciences et techniques en société par le design culturel. C’est dans ce cadre de réalisation pédagogique que sont rassemblés ces textes et documents pour lesquels sont proposés de courtes analyses sur leur fonction de support de diffusion massive dans l’espace public d’une culture populaire et ordinaire des sciences et techniques. Tous ont été rédigés dans le cadre d’un exercice exigé pour la validation d’un enseignement. Si le résultat final peut s’avérer inégalement satisfaisant à l’aune des critères de leurs commanditaires, tous les textes apportent cependant un regard jugé pertinent sur un des aspects des manifestations des sciences et techniques dans leurs rapports à la société au travers de la production et de la consommation culturelle de masse. Quelques-uns ont été un peu remaniés pour la présente édition. Retrouvez-les tous, ainsi que d’autres non publiés dans ce volume, sur le site de la Lucarne : http://ateliercst.hypotheses.org