Deciphering neurodegeneration: models and methods

Published on July 1, 2014   28 min

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Other Talks in the Series: The Genetic Basis of Neurological Disorders

Hello, my name is Patrick Lewis, and I'm an associate professor at the University of Reading, School of Pharmacy. Today, I'm going to discuss some of the model system and methods that we can use to understand neurodegenerative diseases.
The first thing to understand is the scale of the problem that researchers face when trying to dissect the processes that lead to neurodegeneration and neurological disease. This stems from the nature of the organ affected, the brain. The human brain is one of the most complex machines known to man with an estimated 80 billion cells, many forming complex neural networks with multiple other cells. Finding out why some of these cells go wrong is very much analogous to finding a needle in a haystack.
To add to the challenge, there's a huge amount of variation in the types of neurons found in the brain with individual regions, such as midbrain, cerebellum, and frontal cortex, each having a dazzling array of highly specialized neuronal types, illustrated here in a drawing of the human hippocampus by Camillo Golgi. Coupled to this, neurons are only one cell type of many found in the brain. Glial cells such as astrocytes, microglia, oligodendrocytes play a critical role in maintaining neuronal function as well as being central to the processes that lead to neurodegeneration.
The final complicating factor is that there is a broad specificity for a particular region of the nervous system or cell type in different neurodegenerative disorders. In Parkinson's, for example, it is primarily, although not exclusively, dopaminergic neurons in the midbrain that degenerate. There are also particular types of pathology found in different disorders. In amyotrophic lateral sclerosis, or ALS, most of the pathology's in the form of aggregated TPD-43 inclusions in the cytoplasm of cells. How and why are there such exquisite specificity in the etiology of these disorders remains a mystery and is part of the massive challenge faced by researchers in this area.

Deciphering neurodegeneration: models and methods

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