Autophagy Regulation by Lipid Factors with Implications for Parkinson's Disease

Abstract

Parkinson’s disease is the second most common neurodegenerative disorder. It is characterized by the death of dopaminergic neurons in the substantia nigra and a series of debilitating motor symptoms. Macroautophagy (hereafter referred to as autophagy) is a cellular process by which cells degrade proteins, lipids, organelles or dysfunctional components. Autophagy is thought to play an important role in Parkinson’s disease, because it is the only cellular process known to remove large protein aggregates, such as those seen in Parkinson’s disease pathology. Historically, a large body of work has focused on reporting on protein effectors of autophagy, and regulation of autophagy but lipophilic molecules has garnered less attention. This dissertation focuses on the regulatory contributions of lipid molecules to autophagy in addition to describing the identification and lead discovery of autophagy-regulating lipid factors using an endogenous lipid chaperone protein, known as Fatty Acid Binding Protein 5, as a ‘bait’ molecule.