A neurotoxic phosphoform of Elk-1 is implicated in neurodegenerative disease / Anup Sharma.

Format:

Book

Manuscript

Thesis/Dissertation

Author/Creator:

Sharma, Anup.

Contributor:

Eberwine, James H., advisor.

University of Pennsylvania.

Language:

English

Subjects (All):

Penn dissertations--Neuroscience.

Neuroscience--Penn dissertations.

Neurosciences.

Academic Dissertations as Topic.

Medical Subjects:

Neurosciences.

Academic Dissertations as Topic.

Local Subjects:

Penn dissertations--Neuroscience.

Neuroscience--Penn dissertations.

Physical Description:

vii, 116 pages : color illustrations ; 29 cm

Production:

2009.

Summary:

Neurodegenerative diseases are characterized by a number of features including the formation of inclusions, early synaptic degeneration and the selective loss of neurons. Molecules serving as links between these shared features have yet to be identified. Identifying candidates within the diseased microenvironment will open up novel avenues for therapeutic intervention. The transcription factor Elk-1 resides within multiple brain areas both in nuclear and extranuclear neuronal compartments. Interestingly, its de novo expression within a single dendrite initiates neuronal death. Given this novel regionalized function, we assessed whether extranuclear Elk-1 and/or phospho-Elk-1 (pElk-1) protein might be associated with human neurodegenerative disease. We find that the ability of Elk-1 to initiate regionalized neuronal death depends on a specific phosphosite, T417. Furthermore, we find that T417+ Elk-1 uniquely associates with several types of inclusions present in cases of human Lewy body Disease, Alzheimer's disease, and Huntington's Disease. These results provide a molecular link between the presence of inclusions and neuronal loss that is shared across a spectrum of neurodegenerative disease.

Notes:

Adviser: James H. Eberwine.

Thesis (Ph.D. in Neuroscience) -- University of Pennsylvania, 2009

Includes bibliographical references.