{"id":138805,"date":"2021-09-17T15:59:33","date_gmt":"2021-09-17T13:59:33","guid":{"rendered":"https:\/\/www.bordeaux-neurocampus.fr\/friday-seminar-frederic-checler\/"},"modified":"2021-09-21T11:42:59","modified_gmt":"2021-09-21T09:42:59","slug":"friday-seminar-frederic-checler","status":"publish","type":"post","link":"https:\/\/www.bordeaux-neurocampus.fr\/en\/friday-seminar-frederic-checler\/","title":{"rendered":"Friday Seminar – Fr\u00e9d\u00e9ric Checler"},"content":{"rendered":"

Friday 24 September at 11:30<\/strong><\/p>\n

Venue : Centre Broca Nouvelle-Aquitaine<\/strong><\/p>\n

\n

Title<\/h3>\n

Alzheimer\u2019s disease etiology: contribution of APP catabolites distinct from canonical A\u03b2<\/em><\/p>\n

Abstract<\/h3>\n

A\u03b2 has long been at the gravity center of AD pathology. Thus, the amyloid cascade predicts that A\u03b2 accumulation corresponds to the etiological trigger of the disease. However, most of clinical assays aimed at preventing Ab formation or neutralizing it after production have failed so far. We showed that besides A\u03b2, APP-CTF fragments (namely C99) generated by an enzyme called b-secretase could well contribute to the pathology, before any Ab detection and independently of A\u03b2.<\/p>\n

This seminar will gather recent evidences from our laboratory concerning the early presence of C99 in brain, its toxic phenotypes including endolysososmal perturbation and mitochondrial defects, its occurrence in exosomal vesicles and a genetic approach aimed at lowering its production. This seminar will explain the deleterious side-effects observed when targeting g-secretase in vivo<\/em>, that could to some extent account for the drastic alterations observed in clinical trials.<\/p>\n

\n

\"\"<\/a>Fr\u00e9d\u00e9ric Checler<\/span><\/span><\/h3>\n

Universit\u00e9 de Nice-Sophia-Antipolis
\nInstitut de Pharmacologie Mol\u00e9culaire et Cellulaire, CNRS-UMR7275,
\nTeam labeled \u00a0\u00a0\u00ab Fondation pour la Recherche M\u00e9dicale \u00bb\u00a0 et \u00a0\u00ab Laboratoire d\u2019excellence Distalz \u00bb
\nSophia-Antipolis, France<\/p>\n

Page web<\/a><\/p>\n

\n

Invited by Ga\u00ebl Barthet and Christophe Mulle (IINS)<\/em><\/p>\n

Selected publications<\/h3>\n

LAURITZEN, I\u00a0., PARDOSSI-PIQUARD, R., BAUER, C., BRIGHAM, E., ABRAHAM, J.D., RANALDI, S., FRASER, P. St-GEORGE-HYSLOP, P., LE THUC, O., ESPIN, V., CHAMI, L., DUNYS, J. and CHECLER, F<\/strong>. (2012) The b-secretase-derived C-terminal fragment of b-APP, C99 but not Ab, is a key contributor to early intraneuronal lesions in triple transgenic mouse hippocampus. J. Neurosci<\/em>. 32<\/u>, 16243-16255.<\/p>\n

lauritzen, I.,\u00a0 PARDOSSI-PiQUARD, R., BOURGEOIS, A.,PAGNOTTA, S., BIFERI, M-G., BARKATS, M., LACOR, P., KLEIN, W., BAUER, C. and CHECLER F<\/strong> (2016) Intraneuronal aggregation of the b-CTF fragment of APP (C99) induces Ab-independent lysosomal-autophagic pathology. Acta Neuropathol<\/em>. 132, <\/strong>257-276.<\/p>\n

LAURITZEN, I., BECOT, A., BOURGEOIS, A., PARDOSSI-PIQUARD, R., BIFERI, M-G., BARKATS, M. and CHECLER F<\/strong>. (2019) Targeting g-secretase triggers the selective enrichment of oligomeric APP-CTFs in brain extracellular vesicles from Alzheimer cell and mouse models. Translational. Neurodeg<\/em>. 8<\/strong>, 35, doi:10.1186\/s40035-019-0176-6<\/p>\n

VAILLANT-BEUCHOT, L., MARY, A., PARDOSSI-PIQUARD, R., BOURGEOIS, A., LAURITZEN, I., EYSERT, F., KINOSHITA, P.F., CAZARETH, J., BADOT, C., FRAGAKI, K., BUSSIERE, R., MARTIN, C., MARY, R., BAUER, C., PAGNOTTA, S., PAQUIS-FLUCKLINGER, V., BUEE-SCHERRER, V., BUEE, L., LACAS-GERVAIS, S, CHECLER F<\/strong> and CHAMI, M. (2021) Accumulation of amyloid precursor protein C-terminal fragments triggers mitochondrial structure, function and mitophagy defects in Alzheimer\u2019s disease models and human brains . Acta Neuropathologica. <\/em>141<\/strong>, 39-65.<\/p>\n","protected":false},"excerpt":{"rendered":"

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