Friday, February 27th 2015 h. 14,00
Seminars Room, NICO
Linking fatty acid metabolism to peripheral neuropathy
Department of Pharmacological and Biomolecular Sciences, University of Milan
Myelin is a membrane characterized by high lipid content to facilitate impulse propagation. Changes in myelin fatty acid (FA) composition have been associated with peripheral neuropathy, but the specific role of peripheral nerve FA synthesis in myelin formation and function is poorly understood.
We have found that mice lacking sterol regulatory element-binding factor-1c (Srebf1c) have blunted peripheral nerve FA synthesis that results in development of peripheral neuropathy. Srebf1c null mice develop Remak bundle alterations and hypermyelination of small caliber fibers that impair nerve function.
Peripheral nerves lacking Srebf1c show decreased FA synthesis and glycolytic flux, but increased FA catabolism and mitochondrial function. These metabolic alterations are the result of local accumulation of two endogenous peroxisome proliferator-activated receptor-α (Pparα) ligands, 1-palmitoyl-2-oleyl-sn-glycerol-3-phosphatidylcholine and 1-stearoyl-2-oleyl-sn-glycerol-3-phosphatidylcholine. Treatment with a Pparα antagonist rescues the neuropathy of Srebf1c null mice. These findings reveal the importance of peripheral nerve FA synthesis to sustain myelin structure and function.
Host: Alessandro Vercelli
Le ultime novità nella Microscopia Correlativa Multi-modale. Registrazione obbligatoria.
Since 2001, this meeting represented an important event for basic and clinical researchers working on this emerging scientific topic. We will address state-of-the-art approaches in the field of steroids and nervous system, including behavior, epigenetics, genomic and non-genomic actions, the vitamin D, neurodegenerative and psychiatric disorders, and the interference among endocrine disruptors and steroid signaling.
L’inibizione della proteina JNK rallenta la progressione della malattia che colpisce i motoneuroni ed è la prima causa genetica di morte nell’infanzia. Lo dimostra uno studio pubblicato su Frontiers in Molecular Neuroscience dal nostro gruppo di ricerca guidato da Alessandro Vercelli, in collaborazione con l’Istituto Mario Negri di Milano. Chiarire i meccanismi molecolari alla base della SMA può aprire la strada allo sviluppo di nuove terapie.