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NDD: an introduction Definition Neuro: neurones are affected, not necessarily in the brain but also throughout the whole body. Degenerative: The pathological processes lead to degeneration of neuronal tissue. Disease: “A disorder of structure or function in a human, animal, or plant, especially one that produces specific symptoms or that affects a specific location and is not simply a direct result of physical injury” (oxford dictionary).
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Under the supervision of mikls jszbernyi
The physiopathology of Alzheimers disease and other
neurodegenerative disorders Janique de vries Nejla jounadi Chloe
marsollier Under the supervisionof miklsjszbernyi NDD: an
introduction Definition
Neuro: neurones are affected, not necessarily in thebrain but also
throughout the whole body. Degenerative: The pathological processes
lead todegeneration of neuronal tissue. Disease: A disorder of
structure or function in a human,animal, or plant, especially one
that produces specificsymptoms or that affects a specific location
and is notsimply a direct result of physical injury
(oxforddictionary). NDD: an introduction Common pathological
processes (e.g. protein misfolding &mitochondrial dysfunction).
Different clinical outcomes. Photo source :www.cannabisoils.ca NDD:
prevalence Alzheimers disease2010: 35.6 million people
worldwide*2050: million people worldwide* Parkinsons
disease>1/1000 people affected in Europe** Photo source
:www.nyas.org * 2010 report of ADI **European commission site
Questions What are the common characteristics of ndd ?
What does the term implies concerningthe patients prognosis ?
Common pathogenic features
Alzheimers disease Genetic factors Abnormal protein aggregations
Neuroinflammation Mitochondrial dysfunction Oxidative stress
Excitotoxicity Apoptosis Fronto-Temporal dementia Prion diseases
Huntingtons disease Amyotrophic Lateral Sclerosis Parkinsons
disease Spino Cerebellar Ataxias Protein misfolding - Hallmark of
NDDs - Proteinopathies
Alpha helices Beta sheets - Aggregations Amyloid fibrils Plaque
deposits in CNS Impairment of cellular processes Common pathway of
aggregation common mechanism of neurotoxicity Photo source :
Protein misfolding 2 mechanisms : Major consequences :
Spontaneous conformation Induced conformation Different : Brain
location Nerve cells repartition (ECR - ICR - Intra-nuclear) Major
consequences : Interference with axonal transport Apoptosis Gliosis
Inflammation Mitochondrial dysfunctions Controversial causal role
Photo source : Nature Reviews - Neuroscience Mitochondrial
dysfunction
Failure of OXPHOS ATP depletion cell death Abnormal OXPHOS ROS
oxidative stress cell death Mitochondrial damage opening of
mitochondrialpermeability transition pores loss of membrane
potential& pH changes further compromising of OXPHOS Release
ofmitochondrial proteins (SMACs) binding toapoptosis inhibiting
proteins apoptosis Mitochondrial dysfunction
Photo source : "Role of Protein Aggregation in Mitochondrial
Dysfunction and Neurodegeneration in Alzheimers and Parkinsons
Diseases" Hashimoto et al The physiopathology of ALZHEIMERS
DISEASE
And now, an example The physiopathology of ALZHEIMERSDISEASE
Aetiologies 2 protein abnormalities: Mitochondrial
dysfunction:
peptides Senileplaques. Tau protein Neurofibrillary tangles.
Mitochondrialdysfunction: Oxidative stress Tissuedamage. Decreased
glucosemetabolism Photo source : American Health Assistance
Foundation Clinical aspects and treatments
Sporadic AD. Familial AD. Progressive disease Progressive loss
offunction. Cognitive and motorimpairments. TREATMENTS NMDA
antagonists. Cholinesterase inhibitors. AD = major focus ofmedical
research. AD = major issue of publichealth. Common features =
therapeutic targets
Conclusion Common features =therapeutic targets Chlo M. Janique de
V. Nejla J.
THANK YOU FOR YOURATTENTION !