New insights into the pathophysiology of cobalamin deficiency.
Cobalamin-deficient (Cbl-D) central neuropathy in the rat is associated with a locally increased expression of neurotoxic tumour necrosis factor-alpha (TNF-alpha) and a locally decreased expression of neurotrophic epidermal growth factor (EGF). These recent findings suggest that cobalamin oppositely regulates the expression of TNF-alpha and EGF, and raise the possibility that these effects might be independent of its coenzyme function. Furthermore, adult Cbl-D patients have high levels of TNF-alpha and low levels of EGF in the serum and cerebrospinal fluid. Serum levels of TNF-alpha and EGF of cobalamin-treated patients normalize concomitantly with haematological disease remission. These observations suggest that cobalamin deficiency induces an imbalance in TNF-alpha and EGF levels in biological fluids that might have a role in the pathogenesis of the damage caused by pernicious anaemia.
Scalabrino
Giuseppe
G
Institute of General Pathology and Centre of Excellence on Neurodegenerative Diseases, University of Milan, Via Mangiagalli 31, I-20133 Milano, Italy. giuseppe.scalabrino@unimi.it
Peracchi
Maddalena
M
D000752:Anemia, Pernicious / Q000097:blood / Q000134:cerebrospinal fluid / Q000188:drug therapy / Q000378:metabolism*; D000818:Animals; D002490:Central Nervous System / Q000187:drug effects / Q000378:metabolism*; D004195:Disease Models, Animal; D004815:Epidermal Growth Factor / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism; D005743:Gastrectomy; D006801:Humans; D009410:Nerve Degeneration / Q000097:blood / Q000134:cerebrospinal fluid / Q000188:drug therapy / Q000378:metabolism*; D020932:Nerve Growth Factor / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000134:cerebrospinal fluid / Q000378:metabolism; D014805:Vitamin B 12 / Q000494:pharmacology / Q000627:therapeutic use; D014806:Vitamin B 12 Deficiency / Q000097:blood / Q000134:cerebrospinal fluid / Q000188:drug therapy / Q000378:metabolism*
D014409:Tumor Necrosis Factor-alpha; D004815:Epidermal Growth Factor; D020932:Nerve Growth Factor; D014805:Vitamin B 12