Lysosomes are acidic organelles that contain a myriad of hydrolytic enzymes. In neurons, lysosomes traffic throughout the axons and dendrites to deliver catabolic enzymes to distal regions of the cell and maintain local degradative demands. Of the various lysosomal enzymes, glucocerebrosidase (GBA) is of particular interest due to its relationship with synucleinopathies such as Parkinson's Disease and Dementia with Lewy Bodies. Mutations in GBA are the most common genetic risk factor for synucleinopathies, but the mechanistic relationship is unclear. GBA cleaves the glycolipid glucosylceramide (GC) into glucose and ceramide, but mutations in GBA, or its catalytic inhibition, can disrupt the composition of the lysosomal membrane. The lysosomal membrane serves as the platform to which trafficking complexes are recruited and activated. Thus, we investigated if the prolonged catalytic inhibition of GBA by Conduritol B Epoxide (CBE) could interfere with lysosomal trafficking dynamics in axons. In human iPSC-derived cortical neurons treated with CBE for 10 days, we did not observe a change in the motile fraction, velocity, or run length of LAMP1-GFP vesicles. Additionally, we did not find any alterations in lysosomal size or density in the axon, dendrites, or neuronal cell bodies, despite complete inhibition of enzymatic activity. These results suggest that CBE-mediated inhibition of GBA in neurons does not directly impact lysosomal dynamics or size in the time course of our experiments.

Lysosomal transport dynamics in GBA-inhibited iPSC-derived human neurons

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PS-3-C -  Disorders of the Nervous System

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Colleagues and Friends:

I am very happy to welcome you to the 14th annual Canadian Neuroscience Meeting, and to the first virtual edition of our meeting. I want to highlight the important work the CAN meeting chair, **Roger Thompson** and co-chair, **Alyson Fournier**, did to put together the great program we are offering this year. Moving to a virtual format required a complete re-design of the program, and both Roger and Alyson did a splendid job in providing us with an appealing and well adapted program for our first virtual event. I wish to thank them for this very important effort.

Highlights of this year’s scientific meeting include invited speakers **Michael Hausser, Franck Polleux, Gwyneth Card, Magdalena Götz**and Brain Prize winner **Huda Zoghbi**. Plenary and parallel symposia, proposed by our members complete our diverse [scientific program.](https://can-acn.org/meeting-2021/program-2021/)

The 2021 Advocacy session, chaired and organized by CAN advocacy committee chair **Karun Singh**, will feature a special lecture and question period with Member of Parliament and past Science Minister **Kirsty Duncan**. This will be followed by a short overview of CAN’s advocacy activities over the last year. We invite you to participate in this session for insight from Dr. Duncan on the workings of Parliament Hill, and to learn more about what CAN has been doing to promote neuroscience research in Canada.

We are also excited to host **Lisa Willis** in the Equity Diversity and Inclusion session, organized by EDI committee chair **Jibran Khokhar**.

A special highlight of our meeting will be the lectures by award-winning young neuroscientists. We are please to host the CAN 2020 Young Investigator Award winner **Mihaela Iordanova**, and CAN 2021 Young Investigator Award winners **Aaron Phillips** and **Tabrez Siddiqui**. Highlights will also include presentation by the top three winners of the CAN-CIHR-INMHA Brain Star Award winners, **Claire Gizowski, Nuria Daviu Abant** and **Lukas Tamayo-Orrego**.

Independently organized satellite symposia complement and complete this exciting program, check them out here: https://can-acn.org/meeting-2021/2021-satellite-symposia/

Some of the most engaging sessions are always the poster sessions featuring the work of our trainees, so make sure to log in to Gather Town during the poster sessions to chat with the presenters.
We hope you enjoy this program, and look forward to welcoming you, virtually.

Shernaz Bamji

President of the Canadian Association for Neuroscience

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David Vocadlo

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Lysosomal transport dynamics in GBA-inhibited iPSC-derived human neurons

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