A view into Neurodegeneration and
neurodegenerative diseases
Bahareh Eftekharzadeh
Laboratory of Dr. Xavier Salvatella
SemesterI
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Brain With Alzheimer's Disease
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How the Brain and Nerve Cells Change During Alzheimer's Disease
Medical illustration showing how the brain and nerve cells change during
Alzheimer's
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Plaques and Tangles in Alzheimer`s disease
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How the Brain and Nerve Cells Change During Alzheimer's Disease?
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Brain With Parkinson's Disease
Substantia Nigra: substantia nigra appear darker than neighboring areas due to high levels of melanin in
dopaminergic neurons and Parkinson's disease is characterized by the death of dopaminergic neurons in the
substantia nigra.
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How the Brain and Nerve Cells Change During Parkinson's Disease
Medical illustration showing how the brain and nerve cells change during Parkinson's
Comparison between a normal brain and a diseased brain
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Alpha-synuclein aggregates
are responsible for neuronal
dead in brain cells
An example of tremor in Parkinson's Disease
Medical illustration showing how the brain and nerve cells are affected during
Parkinson's
Substantia nigra is an important player in brain function, in particular, in eye
movement, motor planning, reward-seeking, learning.
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Cerebral aggregates in neurodegenerative diseases are toxic.
signature of Alzheimer’s disease:
1.Extracellular amyloid plaques
2.Intracytoplasmic neurofibrillary tangles
Intracytoplasmic aggregates are typically present in the neurons of people affected by
Parkinson’s disease and amyotrophic lateral sclerosis.
Intranuclear inclusions of huntingtin are observed in Huntington’s disease patients and
extracellular prion amyloid plaques that are located in different brain regions are
present in some cases of transmissible spongiform encephalopathy.
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In spite of the different protein compositions, the
ultrastructure of these deposits seems to be similar and
composed mainly of a network of fibrillar polymers.
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Now the question is:
how these aggregates form in the cells
and what initiates the aggregation
formation????
Introduction in protein structure equilibrium
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Schematic representation of the pathway leading to protein misfolding
and aggregation
1.The natively folded protein, normally produced
in diverse cell types, adopts a random coil or αhelical conformation.
2. In the elderly brain, the first pathological step
would be the formation of a misfolded
intermediate that exposed to the aqueous
environment hydrophobic fragments that are
normally buried inside the protein.
3.This intermediate has a high tendency to
aggregate and become stabilized, in a ratelimiting process, by the formation of an
oligomeric β-sheet structure, which by
incorporation of additional monomers gives rise
to protofibrils and finally to cross-β amyloid-like
fibrils.
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Schematic representation of different therapeutic strategies to arrest
protein misfolding and aggregation
1. Stabilization of the folding of the native
protein.
1. Stabilization of the folding of the native protein.
1.
Inhibition and reversal of protein misfolding by
compounds that can specifically destabilize βsheet structures.
1. Competitive
inhibition
of
protein
oligomerization by compounds that bind to the
monomeric protein.
1. Competitive inhibition of aggregation by
molecules that bind to aggregated β-sheets
and block further incorporation of monomers.
2. Increased
clearance
of
the
misfolded/aggregated protein by compounds
that boost clearance mechanisms or decrease
the stability of protein aggregates.
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Different approaches to study Neurodegeneration:
The benefits of animal models for studying the diseases
How can we generate the transgenic animals?
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Different approaches to study Neurodegeneration:
How transgenic animals can be studied in an example?
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Different approaches to study Neurodegeneration:
How transgenic animals can be studied in an example?
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Different approaches to study Neurodegeneration:
2. Biochemical approaches to study neurodegeneration
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What is Alzheimer’s diseases???
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Discussion
How do you see the future of the neurodegenerative disease’s research?
Which approaches will answer more questions?
What is the role of Pharmaceutical companies in developing new drugs?
Who plays more important role in solving the questions in Alzheimr’s
and Parkinson’s diseases? The scientists or industry?
What is your next step, if you would like to stay in this field of research?
…