Chronic ferritin expression within murine dopaminergic midbrain neurons results in a progressive age-related neurodegeneration.
Ferritin elevation has been reported by some laboratories to occur within the substantia nigra (SN), the area of the brain affected in Parkinson's disease (PD), but whether such an increase could be causatively involved in neurodegeneration associated with the disorder is unknown. Here, we report that chronic ferritin elevation in midbrain dopamine-containing neurons results in a progressive age-related neurodegeneration of these cells. This provides strong evidence that chronic ferritin overload could be directly involved in age-related neurodegeneration such as occurs in Parkinson's and other related diseases.
Kaur
Deepinder
D
Buck Institute for Research in Aging, Novato, CA 94945, USA.
Rajagopalan
Subramanian
S
Chinta
Shankar
S
Kumar
Jyothi
J
Di Monte
Donato
D
Cherny
Robert A
RA
Andersen
Julie K
JK
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology; D000367:Age Factors; D000375:Aging; D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D005106:Exploratory Behavior / Q000502:physiology; D005293:Ferritins / Q000235:genetics / Q000378:metabolism*; D005452:Fluoresceins; D015870:Gene Expression / Q000235:genetics; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D051379:Mice; D008822:Mice, Transgenic; D009410:Nerve Degeneration / Q000139:chemically induced / Q000235:genetics / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D009930:Organic Chemicals / Q000378:metabolism; D016622:Silver Staining; D013378:Substantia Nigra / Q000473:pathology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D005452:Fluoresceins; D009930:Organic Chemicals; C435731:fluoro jade; D005293:Ferritins; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine