Publication Date

12-2018

Date of Final Oral Examination (Defense)

11-30-2018

Type of Culminating Activity

Dissertation

Degree Title

Doctor of Philosophy in Biomolecular Sciences

Department

Biology

Supervisory Committee Chair

Brad E. Morrison, Ph.D.

Supervisory Committee Member

Allan Albig, Ph.D.

Supervisory Committee Member

Matthew L. Ferguson, Ph.D.

Supervisory Committee Member

Julia Thom Oxford, Ph.D.

Abstract

Parkinson’s Disease (PD) is an idiopathic disorder with no known cure. With number of cases steadily rising around the world, it is imperative to turn to the underlying cellular and molecular mechanisms of the disease manifestation and neurodegeneration to craft novel modes of therapy. VPS35 is one of the few genes that have identified and definitively linked to familial PD. The particular mutation that has been associated is known to cause dysfunction of a key cellular process known as autophagy. This process is primarily responsible for clearance of unwanted, damaged or misfolded proteins, among other things. Our study reveals an important link between VPS35, PI3K-AKT signaling pathway and autophagy dysfunction that might be a potential mechanism of PD pathogenesis. We also address possible perturbed dopaminergic neurogenesis in the substantia nigra brain region as a second plausible disease mechanism, as well as a target for therapeutic intervention.

DOI

10.18122/td/1488/boisestate

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