Ataxia Telangiectasia (AT)

Project overview

Another aspect of glial biology is the role of astrocytes in establishing supportive CNS environments. We became interested in understanding the role of astrocytes in the rare but devastating genetic disease Ataxia telangiectasia (AT). AT is an autosomal recessive disorder caused by mutations in the ATM gene and is characterized by crippling ataxia beginning in late infancy followed by progressive CNS degeneration. The cerebellar cortex of AT patients appears to be the initial site of deterioration with apoptosis and necrosis of Purkinje neurons, and to a lesser extent, granular neuron. While the majority of research has been focused on the neuronal cell population affected in AT, there is now increasing awareness of glial contribution to proper CNS function. It is has been shown that many CNS disorders display primary and secondary glial impediments which result in neuronal dysfunction and death. For example, astrocytes, are the major means of combating oxidative stress in the CNS by removing oxidizing neurotransmitters from synapses and providing critical anti-oxidative compounds to neurons. In addition to the role of astrocytes in oxidative stress regulation they are a pivotal component of the blood-brain barrier and due to their location are responsible for nutrient transport in addition to direct roles in neurotransmission and maintenance of both synaptic and non-synaptic microenvironments. In light of this information, we began to determine the extent of glial dysfunction on the progression of AT. Our result indicate that astrocytic function is severely impaired in AT CNS tissue and we show that AT mutant astrocytes are unable to maintain neuronal integrity and survival. This new discovery opens the possibility for generating new therapeutic strategies that target the dysfunction astrocytes in order to halt or abolish neuronal degeneration.

In addition to determining the cell populations that are targets of specific disease, we also have a interest in precursor cells and their role in repair.

Contact

Margot Mayer-Pröschel
University of Rochester
Box 633
601 Elmwood Ave.
Rochester, NY 14642
Office: MRB 2-9627
+1-585-273-1449
margot_mayer-proschel@urmc.
rochester.edu

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