This course provides an in-depth description of neurodegenerative processes that occur during the development of neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease and Huntington’s disease, which are some of the most debilitating disorders that a person can have. Although clinical manifestations of these neurodegenerative diseases are different, they share common features in neuropathology and in the underlying molecular mechanisms. Since they share inclusions (e.g. plaques and tangles) with accumulations of aberrant proteins, the modern terminology for these diseases is conformational diseases. The aim of this course is to gain insight into the mechanisms of neurodegenerative processes, such as the deposition of aggregated proteins, the loss of neurons and synapses, alterations in neurogenesis and inflammatory processes, alterations in metabolic/oxidative state and discussion over whether these are the cause or consequence of the disease. Moreover, this course covers the influences of genetic and environmental factors on disease progression and strategies for therapy. Major emphasis is on the molecular, i.e. the neurochemical and neurobiological mechanisms that affect disease progression. Transgenic animal models as well as brain cell cultures are used to study these.
Doelstellingen van dit vak
Knowledge of: Tauopathies: Alzheimer’s disease (AD), Frontal tempolar dementia, Progressive supranuclear palsy, Pick’s disease, Argyrophilic grain disease, Synucleinopathies: Parkinson disease, Multisystem atrophy. Polyglutamine diseases: Huntington, and Spinocerebellar ataxias. Mixed pathogies; Diffuse Lewy body disease, Number of affected persons; World wide, USA and The Netherlands, early and late onset AD, Aging, Amyloid beta cascade hypothesis, amyloid precursor protein, Presenelin 1 and 2, Tau, ubiquitin, ApoE polymorphism, risk factors, oxidative stress, loss of synapses, energy metabolism, plaques, tangles, neuronal loss, gliosis, cytoarchitecture of hippocampus and neocortex.
Laboratory skills are recommended
• Van Leeuwen et al., Frameshift mutants of amyloid precursor protein and ubiquitin-B are prominent in Alzheimer and Down patients. Science 279, 242-247, 1998 • Irmler, M., et al., Long-term proteasomal inhibition in transgenic mice by UBB+1 expression results in dysfunction of central respiration control reminiscent of brainstem neuropathology in Alzheimer patients, Acta Neuropathologica, 124, 197-197, 2012 • Mucke, L., and Selkoe D.J. Neurotoxicity of Amyloid β-protein: Synaptic and Network Dysfunction, Cold Spring Harbor Perspectives in Medicine 1-17, 2012