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Event Type:  Seminar (This is an NIH Science event)
Title:  Neurobiology Interest Group Seminar Series: "The secret life of active axonal lysosomes in health and neurodegeneration"
Description:  Lysosomes serve as degradation hubs for the autophagic and endocytic pathways, thus maintaining cellular homeostasis crucial for neuron growth, synaptic function, and survival. Emerging genetic and pathological evidence implicates lysosomal deficits in the pathogenesis of major neurodegenerative diseases, including Parkinson’s and Alzheimer’s. Axonal pathology occurs in neurodegenerative diseases caused by genetic defects in lysosomal proteins, highlighting the importance of proper lysosomal function in maintaining axonal health. With these clinical implications, there is a growing interest in understanding the causal relationship between an impaired lysosome system and disease progression. Neurons are highly polarized cells with a thin long axon, and thus face exceptional challenges to maintain cellular homeostasis in distal axons. While enzymatically active lysosomes are enriched in the soma, their distribution and motility patterns, as well as their delivery to distal axons in health and neurodegenerative diseases remain largely unkown. We developed a unique approach to study lysosome trafficking and function in distal axons of live neurons cultured in microfluidic devices. Rather than using the commonly-used endo-lysosomal marker LAMP1, we applied multiple activity-based fluorescent probes to label enzymatically active lysosomes. Our study demonstrates that active lysosomes move bi-directionally in distal axons, constantly surveying the axonal cytoplasm in healthy neurons. They are robustly delivered from the soma to distal axons and growth cones, where they fuse with autophagosomes and perform local cargo degradation. Importantly, lysosome delivery to distal axons is significantly impaired in mutant neurons isolated from adult symptomatic Niemann-Pick disease type C (NPC) mice, a lysosome-linked neurodegenerative disease characterized by axonal dystrophy. Our study reveals fundamental aspects of the axonal lysosomal system and provides some of the first insight
Series Name:  Neurobiology Interest Group Seminar Series
Event URL:
Videocast:  Event will not be videocast
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Thursday, June 07, 2018   3:00pm - 5:00pm Add To Outlook Calendar     Add To iCal Calendar     Add To Entourage Calendar
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Name:   Tamar Farfel-Becker
Title:   PhD
Organization:   NINDS
City/Province:   Bethesda
State:   Maryland

Organization(s):  [NIH] Neurobiology Interest Group

Location:  On the main NIH Campus
Building:  Building 40
Room:  1201/1203
Street Address:  40 Convent Drive
City:  Bethesda
State:  Maryland
Zip Code:  20892

Name:   Richa Lomash
Name:   Shireen Sarraf
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