Dr. Albert La Spada

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Deconstructing Neurodegenerative Proteinopathies: From Pathology of Neuron Demise to Therapeutic Interventon

Dr. Albert La Spada
 Pathology; Neurology
University of California, Irvine

Date: Tuesday, June 14
Time: 12:00 p.m. – 1:00 p.m.

 ** This is a hybrid event** 

Abstract:Both rare inherited neurodegenerative disorders and common sporadic neurodegenerative diseases are caused by misfolded proteins that accumulate in neurons and glia of affected patients.  The CAG – polyglutamine (PolyQ) repeat diseases are one category of inherited neurodegenerative disorders that are caused by the expansion of a CAG triplet repeat, resulting in a protein with an abnormally extended polyglutamine (polyQ) tract.  The repeat expansions in these diseases occur in the coding region, and lead to the production of aggregate-prone proteins.  Of the nine CAG-PolyQ diseases, I have been studying the disease pathogenesis of three such disorders: X-linked spinal & bulbar muscular atrophy (SBMA/Kennedy’s disease), Huntington’s disease, and spinocerebellar ataxia type 7.  To determine the cellular and molecular basis of these diseases, I have relied upon mouse models and human stem cell models, and through these efforts, I have uncovered a central role for transcription dysregulation, altered proteostasis, and bioenergetic abnormalities in the pathogenesis of these disorders.  Unbiased transcriptome analysis and directed studies of cell-type contribution have yielded crucial insights into the nature of these diseases, and have revealed targets and pathways likely amenable to therapeutic manipulation.