Dalmo Mendonca Neuroscience April 1st, 2011.  What is up with polyglutamine?  Cerebellar Ataxia & Digestion?  Is stem cell treatment within our reach?

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Presentation transcript:

Dalmo Mendonca Neuroscience April 1st, 2011

 What is up with polyglutamine?  Cerebellar Ataxia & Digestion?  Is stem cell treatment within our reach?

 Mutations that cause repeat Gln in ATXN1  Huntington’s, SCA-1, other diseases  Knockout mice with polyglutamine seq. No ataxia! (at least not immediately) How is ATXN1 being regulated? Answer: Phosphorylation of Ser(776)

 Gluten Sensitivity & Celiac Disease Inappropriate autoimmune response Usually manifested in the intestines In some patients, gluten ingestion can impair the cerebellum and kill Purkinje cells  Refsum Disease Inability to digest phytanic acid Accumulation  Plaque  Neuropathy Seen in last week’s episode of House

 Purkinje cell death leads to ataxia Get new ones!  Embryonic stem cells is an option Done in mice Insulin, cyclopamine, & fibroblast GF1  Secret recipe for mature Purkinje cells Results in as little as one week  Where do we go from here?

 Serine 776 of Ataxin-1 Is Critical for Polyglutamine-Induced Disease in SCA1 Transgenic Mice  Ataxia with loss of Purkinje cells in a mouse model for Refsum disease.  Ontogeny-recapitulating generation and tissue integration of ES cell–derived Purkinje cells