Elucidating the Role of Reactive Oxygen Species on Dopamine 𝛽-Hydroxylase Activity and Aggregation

Shivam Dewan

Abstract

Dopamine 𝛽-Hydroxylase (DBH) is a copper-containing monooxygenase that catalyzes the hydroxylation of dopamine to norepinephrine.¹ Deficiency of norepinephrine, a neurotransmitter important for the modulation of nervous system functions such as attention, arousal, and cognition, learning, and memory has ties to the progression of neurodegenerative diseases such as Alzheimer’s (AD) and Parkinson’s disease (PD).² Evidence shows that AD and PD both may be caused through DBH dysfunction through either degeneration of locus coeruleus (LC) noradrenergic neurons, neuroinflammation, or dysregulation of metals such as copper and iron.^{2, 3, 4} Overproduction of reactive oxygen species can lead to the irreversible oxidation of proteins which can affect cell homeostasis.⁵

Exposure to ROS may alter DBH activity and lead to aggregation.⁶ For both AD and PD, the aggregated misfolded proteins are specific to each in that for AD, the hallmarks include 𝛽- amyloid and tau protein aggregates while in PD, the hallmarks include aggregated 𝛼-synuclein in Lewy bodies.⁵ Through use of a colorimetric assay using DMPD and peptide identification by mass spectrometry, we investigated how metal oxidative conditions impacted DBH.