Expression of lactoferrin receptors is increased in the mesencephalon of patients with Parkinson disease.
The degeneration of nigral dopaminergic neurons in Parkinson disease is believed to be associated with oxidative stress. Since iron levels are increased in the substantia nigra of parkinsonian patients and this metal catalyzes the formation of free radicals, it may be involved in the mechanisms of nerve cell death. The cause of nigral iron increase is not understood. Iron acquisition by neurons may occur from iron-transferrin complexes with a direct interaction with specific membrane receptors, but recent results have shown a low density of transferrin receptors in the substantia nigra. To investigate whether neuronal death in Parkinson disease may be associated with changes in a pathway supplementary to that of transferrin, lactoferrin (lactotransferrin) receptor expression was studied in the mesencephalon. In this report we present evidence from immunohistochemical staining of postmortem human brain tissue that lactoferrin receptors are localized on neurons (perikarya, dendrites, axons), cerebral microvasculature, and, in some cases, glial cells. In parkinsonian patients, lactoferrin receptor immunoreactivity on neurons and microvessels was increased and more pronounced in those regions of the mesencephalon where the loss of dopaminergic neurons is severe. Moreover, in the substantia nigra, the intensity of immunoreactivity on neurons and microvessels was higher for patients with higher nigral dopaminergic loss. These data suggest that lactoferrin receptors on vulnerable neurons may increase intraneuronal iron levels and contribute to the degeneration of nigral dopaminergic neurons in Parkinson disease.
Faucheux
B A
BA
Institut National de la Santé et de la Recherche Médicale, Unité 289, Hôpital de la Salpêtrière, Paris, France.
Nillesse
N
N
Damier
P
P
Spik
G
G
Mouatt-Prigent
A
A
Pierce
A
A
Leveugle
B
B
Kubis
N
N
Hauw
J J
JJ
Agid
Y
Y
D000368:Aged; D000369:Aged, 80 and over; D000918:Antibody Specificity; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D007781:Lactoferrin / Q000378:metabolism*; D008833:Microcirculation / Q000737:chemistry / Q000166:cytology; D009457:Neuroglia / Q000737:chemistry / Q000166:cytology; D009474:Neurons / Q000737:chemistry / Q000166:cytology; D010300:Parkinson Disease; D011956:Receptors, Cell Surface / Q000032:analysis* / Q000276:immunology; D013378:Substantia Nigra / Q000098:blood supply / Q000737:chemistry* / Q000166:cytology
D011956:Receptors, Cell Surface; C038340:lactoferrin receptors; D007781:Lactoferrin