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.
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