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Printable Handouts
Navigable Slide Index
- Introduction
- Outline
- Lysosomes
- Pathways that converge on lysosomes
- Lysosomal dependent cell death
- Lysosomal membrane permeabilization (LMP)
- Methods to assess LMP
- Inhibitors of LCD
- Physiological functions of LCD: mammary gland involution & neutrophils
- Physiological functions of LCD: bacterial & HIV infection
- Examples of LCD and neurodegeneration (1)
- Examples of LCD and neurodegeneration (2)
- Retinitis pigmentosa
- Photoreceptor cell death from P20
- Caspase-independent cell death in the Rd10 mouse
- Rd10 retinas display reduced/diffuse cathepsin B staining
- Rd10 retinas display increased Cathepsin B activity
- What is inducing lysosomal membrane permeabilization?
- Calpain and cathepsin inhibitiors rescue phenotype rd10 in vivo: P19-P21
- Calpain and cathepsin inhibitiors rescue phenotype rd10 in vivo: P23-P25
- Rd10 retinas display a block in autophagy flux
- Rd10 phenotype can be mimicked incubating wildtype retinas with calcium ionophore A23187 (1)
- Rd10 phenotype can be mimicked incubating wildtype retinas with calcium ionophore A23187 (2)
- Protease inhibitors rescue A23187 induced cell death: E64d & L/P
- Protease inhibitors rescue A23187 induced cell death: Wortmannin
- Cell death is increased with autophagy inductors and inhibited with protease inhibitors in rd10 mice
- Conclusion – Retinitis pigmentosa 1
- Neuroprotective strategies
- Models of lysosomal dysfunction and neurodegeneration
- Acknowledgements
Topics Covered
- Definition and functions of lysosomes
- Lysosomes and their role in cell death (LCD)
- Lysosomal membrane permeabilization (LMP)
- Methods to assess LMP
- Inhibitors of LCD
- Physiological examples of LCD
- LCD in neurodegeneration
- Lysosomes and cell death during retinal degeneration
- Neuroprotective strategies
Links
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Talk Citation
Boya, P. (2020, February 27). Lysosome damage and autophagy during neurodegenerative conditions [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved November 5, 2024, from https://doi.org/10.69645/MBHN3222.Export Citation (RIS)
Publication History
Financial Disclosures
- There are no commercial/financial matters to disclose.
Other Talks in the Series: Autophagy and Lysosomal Storage Diseases
Transcript
Please wait while the transcript is being prepared...
0:00
My name is Patricia Boya.
I work at CIB-CSIC in Madrid, Spain.
The title of my talk is "Lysosomal Damage and
Autophagy During Neurodegenerative Conditions".
0:12
So this is the outline of today's talk.
First, I will be introducing lysosomes and give the definition and functions.
Then I will go to talk about lysosomes and cell death,
and how lysosomal membrane permeabilization induces cell death.
Methods to assess lysosomal membrane permeabilization.
Inhibitors of lysosomal cell death.
Then we'll give some examples of physiological examples of lysosomal cell death.
Then I will talk about lysosomal cell death during neurodegeneration,
and then give you a specific example of work done in
our lab regarding lysosomes and cell death during retinal degeneration.
I will finish my talk talking about neuroprotective strategies for lysosomal cell death.
0:56
This image displays the cells lysosomes
labeled in red after staining with the dye Acridine orange.
Lysosomes are membrane-bound organelles that are found in our cells.
They have an acidic pH that is maintained by the vacuolar ATPase.
Lysosomes are filled of acidic hydrolases such as proteases,
lipases, and DNAases that are in charge of the control digestion of macromolecules.
1:22
Depending on how the material to be degraded reaches the lysosomes,
we can distinguish between heterophagy,
when it is extracellular material,
and autophagy, when the material to be degraded comes from the inside of the cell.
Heterophagy delivers the lysosome material for degradation,
such as bacteria and apoptotic cells.
Autophagy is classified into several forms.
Macroautophagy, which is characterized by the formation of an intermediate organelle,
the autophagosome, which enwraps cytoplasmic component including entire organelles.
Then the good material is then degraded upon fusion of the autophagosome with a lysosome.
In chaperone-mediated autophagy, proteins bearing the KFERQ motif are
specifically delivered to the lysosome via
interaction with the chaperone proteins, such as Hsp70.
This molecule in turn interacts with LAMP-2A,
a receptor found on the lysosomal membrane,
and triggers the unfolding and translocation of the protein inside the lysosomal lumen.
Finally, microautophagy involves the direct transportation
into the lysosome of molecules selected for degradation.