Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

Neurodegeneration is a prominent feature of the gangliosidoses, a group of lysosomal storage diseases. Here we show altered iron homeostasis in mouse models of both GM1 and GM2 gangliosidoses, which are characterized by progressive depletion of iron in brain tissue. This finding contrasts with the findings in many other neurological disorders, where excess iron deposition has been reported. We found that key regulators of iron homeostasis, hepcidin and IL-6, were increased in gangliosidoses mice. In the brain, the principal iron transport and delivery protein transferrin was reduced, accompanied by a progressive inability of the brain to acquire iron from the circulation. Expression of the transferrin receptor was up-regulated reciprocally. Despite the deregulation of iron homeostasis administration of iron prolonged survival in the diseased mice by up to 38%, with onset of disease delayed and motor function preserved.

Type

Journal article

Journal

Neurobiol Dis

Publication Date

06/2009

Volume

34

Pages

406 - 416

Keywords

Age of Onset, Animals, Antimicrobial Cationic Peptides, Blood Chemical Analysis, Brain, Disease Models, Animal, Gangliosidoses, GM2, Gangliosidosis, GM1, Hepcidins, Hexosaminidase B, Homeostasis, Interleukin-6, Iron, Mice, Mice, Knockout, Mitochondria, Motor Activity, Receptors, Transferrin, Transferrin, Treatment Outcome, beta-Galactosidase