Immune-labelling combined with imaging MS has provided the first direct evidence of an iron–dopamine interaction in Parkinson's © Shutterstock
Neuron death is an obvious aspect of neurodegenerative disease but a complex puzzle of biological pathways and interactions needs to be teased apart to understand the underlying mechanisms.
Philip Doble, of the University of Technology in Sydney, Australia, and colleagues have unveiled an immune-labelling and imaging mass spectrometry technique to demonstrate the interaction of iron and dopamine in the brain of a Parkinson’s disease (PD) mouse model. They hope their findings may bring researchers closer to understanding and treating this debilitating condition.
PD is caused by the degeneration of dopaminergic neurons in the substantia nigra (SN) region of the brain, causing loss of function, in particular that linked with movement. Iron is known to be present in higher concentrations in the brains of PD patients. ‘We don’t know for certain if this is a cause or consequence of the disease,’ explains Doble, ‘but increasing evidence is pointing to iron playing a major role in the death of dopamine-producing neurons of the SN.’ The interaction of iron and dopamine has been proposed as a neurotoxic mechanism through a redox-couple, which produces free radicals; however, this interaction has proved difficult to study in situ.
By targeting tyrosine hydroxylase (TH), an enzyme involved in dopamine biosynthesis, using a metal-linked immunohistochemical approach, the team successfully quantified the co-localisation of TH and iron in the brain through simultaneous imaging of the two species in a PD model, providing the first direct evidence of this relationship.
Read the full article in Chemistry World»
Read the original journal article in Chemical Science:
An iron-dopamine index predicts risk of parkinsonian neurodegeneration in the substantia nigra pars compacta
Dominic J. Hare, Peng Lei, Scott Ayton, Blaine R Roberts, Rudolf Grimm, Jessica L. George, David Bishop, Alison Beavis, Sarah J. Donovan, Gawain McColl, Irene Volitakis, Colin L. Masters, Paul A. Adlard, Robert A Cherny, Ashley Ian Bush, David I Finkelstein and Philip Doble
Chem. Sci., 2014, Accepted Manuscript, DOI: 10.1039/C3SC53461H, Edge Article
