Spirochetes are suspected to be linked to the genesis of neurological diseases, including neurosyphillis
or neurodegeneration (ND). Impaired iron homeostasis has been implicated in loss of function in
several enzymes requiring iron as a cofactor, formation of toxic oxidative species, inflammation and elevated
production of beta-amyloid proteins. This review proposes to discuss the link that may exist between
the involvement of Treponema spp. in the genesis or worsening of ND, and iron dyshomeostasis.
Proteins secreted by Treponema can act directly on iron metabolism, with hemin binding ability (HbpA
and HbpB) and iron reductase able to reduce the central ferric iron of hemin, iron-containing proteins
(rubredoxin, neelaredoxin, desulfoferrodoxin metalloproteins, bacterioferritins etc). Treponema can also
interact with cellular compounds, especially plasma proteins involved in iron metabolism, contributing to
the virulence of the syphilis spirochetes (e.g. treponemal motility and survival). Fibronectin, transferrin
and lactoferrin were also shown to be receptors for treponemal adherence to host cells and extracellular
matrix. Association between Treponema and iron binding proteins results in iron accumulation and
sequestration by Treponema from host macromolecules during systemic and mucosal infections.