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SUMMARY:The Lysosome: Hub for α-Synuclein Aggregation and Degradation?
DTSTART:20231123T100000
DTEND:20231123T110000
DTSTAMP:20260510T094855Z
UID:b59c8f5d408ab95dccf679f9a5b23a5bb37b1a53d37e947fc63b7f40
CATEGORIES:Conferences - Seminars
DESCRIPTION:Prof. Friederike Zunke\, Group Leader\, Department of Molecul
 ar Neurology\, University Hospital Erlangen / FAU Erlangen-Nürnberg (Germ
 any)\nBIOENGINEERING SEMINAR\n \nAbstract:\nSynucleinopathies are neurode
 generative disorders characterized by the abnormal intracellular accumulat
 ion of α-synuclein (aSyn)\, including Parkinson’s disease (PD) as well 
 as Multiple System Atrophy (MSA). While the exact mechanisms underlying aS
 yn pathology have not been fully understood\, increasing evidence suggests
  the involvement of autophagic as well as lysosomal pathways to disease pa
 thology\, especially for PD. Our studies focus on the effect of aSyn aggre
 gates on lysosomal function and turnover\, particularly focusing on lysoso
 mal transport and homeostasis.  Since lysosomal enzymes comprising cathep
 sins have been shown to be directly involved in the lysosomal degradation 
 of aSyn\, impairment of their enzymatic capacity has extensive consequence
 s.\nFurther\, we propose the lysosome and its enzymes (in particular cathe
 psins) as therapeutic target for synucleinopathies. Hence\, strategies to 
 increase lysosomal trafficking and direct application of aSyn-degrading ly
 sosomal enzymes (cathepsins) are tested to evaluate the effects on aSyn pa
 thology and neuronal function.\nIn our studies\, we apply state-of-the-art
  technology of induced pluripotent stem cells (iPSC) of PD patients and mo
 use models harboring aSyn pathology. aSyn conformers and their effects on 
 cellular homeostasis and lysosomal function was evaluated by biochemical a
 nalyses as well as intracellular lysosomal live-cell assays.\nIn patient-d
 erived dopaminergic neurons and a mouse model harboring aSyn aggregation\,
  we show that lysosomal trafficking of cathepsins as well as b-glucocerebr
 osidase (one of the highest genetic risk factors to develop PD) is impaire
 d\, resulting in reduced proteolytic activity of these enzymes in the lyso
 some. Our studies show that boosting lysosomal function\, e.g. vis the adm
 inistration of recombinant human proforms of cathepsins (CTSD and CTSB) re
 sults in a decrease of pathology-associated aSyn and restores neuronal fun
 ction.\nAltogether\, our findings demonstrate a strong interplay between a
 Syn aggregation pathways and function of lysosomal enzymes. It appears tha
 t aSyn interferes with the enzymatic function of cathepsins leading to a v
 icious cycle of impaired aSyn degradation.\n\nBio:\nProfessor Friederike Z
 unke obtained a Bachelor’s degree in biochemistry at the University of K
 iel (Kiel\, Germany) and a Master’s degree in biomedical sciences at the
  St. George’s University (London\, UK). She received a PhD from the bioc
 hemical department at the University of Kiel in 2015 for work focused on i
 ntracellular mechanisms and the role of lysosomal dysfunction in neurodege
 neration. She continued to work on lysosomal pathways and alpha-synuclein 
 aggregation processes during her postdoctoral training in the department o
 f neurology of the Northwestern University in Chicago. In 2016\, she began
  work as an independent group leader in the Institute of Biochemistry at t
 he University of Kiel (Germany)\, and in 2020 she was appointed as junior 
 professor for translational neurosciences in the department of molecular N
 eurology at the University Hospital Erlangen\, where she and her group con
 tinue to work on molecular and structural mechanisms of Parkinson’s dise
 ase.\n\n\n\n\nZoom link for attending remotely: https://epfl.zoom.us/j/615
 09627308
LOCATION:AI 1153 https://plan.epfl.ch/?room==AI%201153 https://epfl.zoom.u
 s/j/61509627308
STATUS:CONFIRMED
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