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Printable Handouts
Navigable Slide Index
- Introduction
- Disclosures
- Plan (1)
- Jean-Martin Charcot
- Motor neurons
- Motor neuron disease/ amyotrophic lateral sclerosis
- ALS/MND is heterogeneous
- Clinical heterogeneity of MND
- Genetic heterogeneity
- Pathological heterogeneity
- Pathological heterogeneity of MND
- Pathology in the spinal cord
- Motor neuron disease prognosis
- Complex pathophysiology of MND
- Plan (2)
- Oxidative stress
- Sources of intracellular oxidative stress
- Mitochondria: energy generators of the cell
- Mitochondrial free radical production
- The mitochondrial electron transport chain
- Intracellular reactive oxygen species (ROS)
- ROS and oxidative damage
- Plan (3)
- Anti-oxidant defence mechanisms
- Nrf2 – anti-oxidant response – “programmed cell life pathway”
- Mitochondrial anti-oxidant defence
- Plan (4)
- At least 30 genes known to cause/predispose to MND
- Cu/Zn SOD1 gene and protein
- SOD1 mutations
- SOD1 mutations: toxic gain of function of mutant protein (1)
- SOD1 mutations: toxic gain of function of mutant protein (2)
- Multiple mechanisms contribute to MN injury in ALS: lessons from SOD1
- Identification of the SOD1 gene allowed MND disease modelling
- NSC34 cell model
- Use of the NSC34 cell model to identify and ameliorate pathways leading to motor neuron injury
- Mitochondrial morphology in NSC34 MN cells
- Mitochondrial complex activity
- How does mutant SOD1 exert a neurotoxic effect through mitochondria?
- Oxidative stress measured by dichlorofluorescein (DCF) in NSC34 cells
- DCF assay validation
- Protective effect of ebselen on oxidative stress in NSC34 cells: reduction in DCF fluorescence
- Mitochondrial dysfunction in mutant SOD1 G93A mice
- Gene Expression Profiling (GEP) in MND
- Understanding the pathways to motor neuron injury using gene expression profiling
- Headlines from transcriptomics studies of motor neurons in health and disease
- Anti-oxidant related (“programmed cell life”) genes and pathways
- Nrf2 – anti-oxidant response – “programmed cell life pathway”
- Evidence that dysregulation of Nrf2/ARE plays a role in MND
- SOD1 G93A transgenic mouse model of ALS
- Clinical and neuropathological progression of disease in transgenic SOD1G93A mice
- SOD1 mutant transgenic mice: evidence for oxidative damage
Topics Covered
- Introduction to Amyotrophic Lateral Sclerosis (ALS)/Motor Neuron Disease (MND)
- Clinical genetic and pathological heterogeneity of MND
- Mechanisms of neuronal oxidative stress
- Mitochondria oxidative stress response
- Antioxidant defence mechanisms
- Evidence for the role of oxidative stress in SOD1 MND
- The role of Nrf2 in MND
Links
Series:
Categories:
Therapeutic Areas:
Talk Citation
Shaw, P. (2022, September 29). Oxidative stress in amyotrophic lateral sclerosis (ALS) 1 [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved December 14, 2024, from https://doi.org/10.69645/XYGL8120.Export Citation (RIS)
Publication History
Financial Disclosures
- Prof. Dame Pamela Shaw has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.
Oxidative stress in amyotrophic lateral sclerosis (ALS) 1
Published on September 29, 2022
33 min
Other Talks in the Series: ALS and Other Motor Neuron Disorders
Transcript
Please wait while the transcript is being prepared...
0:00
My name is Professor
Dame Pamela Shaw.
I'm from the Neurology
Department at
the University of Sheffield and
the Sheffield Institute for
Translational Neuroscience.
The topic of my lecture
is Oxidative Stress
in Amyotrophic Lateral
Sclerosis (ALS).
0:21
I have no disclosures
relevant to this lecture.
0:27
What I'm going to cover
during the lecture
is on these seven areas.
First of all, I'm
going to introduce you
to Motor Neuron Disease or ALS,
then I will cover the mechanisms
of neuronal oxidative stress,
and then discuss antioxidant
defence mechanisms.
I will then go over the
evidence for the role of
oxidative stress in
SOD1-related MND.
Then cover the evidence
for oxidative stress
in other sub-types
of this disease.
I'll then review the causes
of oxidative stress in MND,
and in the final
section talk about
oxidative stress as a
potential therapeutic target.
1:15
ALS or Motor Neuron Disease
was first described by
the French physician,
Jean-Martin Charcot, at
the Salpetriere Hospital,
in Paris in 1869.
1:29
What motor neurons
do, in a nutshell,
is form a communication between
the brain and the muscle.
We have this beautiful
network of processes or axons
from motor neurons
that come out from
the central nervous system
into the peripheral nerves
and form a contact eventually
with muscle fibres.
Motor neurons are the
largest cells in the body.
They may have an axon up
to a metre in length,
if you think about
a motor neuron in
the lower spinal
cord connecting with
a muscle in the lower
part of the leg,
and so they're very
large, specialised cells
with very long processes.
If you imagine the
size of the cell body
as being the size
of a tennis ball,
if you transpose it
in your mind's eye,
then the relevant axon would be
up to 2 kilometres in length.
Amazing cells with
amazing properties.