Home >> Neurological Research, Volume 29, Number 1

Activation of the RAGE pathway: a general mechanism in the pathogenesis of polyneuropathies?

Authors: Haslbeck, Karl Matthias1; Neundörfer, Bernhard1; Schlötzer-Schrehardt, Ursula2; Bierhaus, Angelika3; Schleicher, Erwin4; Pauli, Elisabeth1; Haslbeck, Manfred5; Hecht, Martin1; Nawroth, Peter3; Heuss, Dieter1

Source: Neurological Research, Volume 29, Number 1, January 2007 , pp. 103-110(8)

Publisher: Maney Publishing

Buy & download fulltext article:

OR

Price: $48.00 plus tax (Refund Policy)

Abstract:

Objectives: Binding of ligands to the receptor for advanced glycation end products (RAGE) results in activation of the transcription factor NF-?B and subsequent expression of NF-?B regulated cytokines and is a possible pathomechanism in diabetic and in vasculitic polyneuropathies (PNP). We wanted to investigate whether the newly discovered RAGE pathway also contributes to the pathogenesis of various other PNP.

Methods: The presence of the RAGE ligand N ? -Carboxymethyllysine (CML), the receptor itself and NF-?Bp65 was studied in sural nerve biopsies of patients with alcohol-associated PNP (n = 5), PNP owing to vitamin B12 deficiency (n = 5), chronic inflammatory demyelinating PNP (CIDP, n = 10), Charcot-Marie-Tooth disease (CMT) I or II (n = 10), PNP caused by monoclonal gammopathy of unknown significance (MGUS) (n = 5), idiopathic PNP (n = 10) and five normal controls by immunohistochemistry. Biopsies of either ten patients with diabetic and vasculitic PNP served as positive controls.

Results: CML, RAGE and NF-?Bp65 were found in co-localization in epineurial vessels in PNP owing to vitamin B12 deficiency, diabetes and vasculitis and in the perineurium in diabetic PNP, vasculitic PNP and in some cases in CIDP and vitamin B12 deficiency. Only diabetic subjects demonstrated co-expression of the three antigens in endoneurial vessels. Increased CML, RAGE and NF-?Bp65 expression was detected in endoneurial and epineurial mononuclear cells in CIDP and in vasculitic PNP. Additionally, RAGE expression in Schwann cells was significantly increased in diabetic PNP.

Discussion: These data suggest that activation of the RAGE pathway might contribute to the pathogenesis of CIDP, PNP owing to vitamin B12 deficiency, diabetes and vasculitis, whereas it does not seem to be involved in the pathogenesis of PNP owing to alcohol, MGUS, CMT I or II and idiopathic PNP.

Keywords: NF-KAPPAB; NEPSI-CARBOXYMETHYLLYSINE; POLYNEUROPATHIES; RAGE

Document Type: Research Article

DOI: http://dx.doi.org/10.1179/174313206X152564

Affiliations: 1: Department of Neurology, University Erlangen/Nürnberg, Schwabachanlage 6, 91054 Erlangen, Germany 2: Department of Ophthalmology, University Erlangen/Nürnberg, Schwabachanlage 6, 91054 Erlangen, Germany 3: Department of Medicine I, University Heidelberg, Im Neuenheimer Feld 410, 69120 Heidelberg, Germany 4: Department of Medicine IV, University Tübingen, Ottfried-Müllerstr. 10, 72076 Tübingen, Germany 5: Diabetes Research Institute, Kölner Platz 1, 80804 München, Germany

Publication date: 2007-01-01

More about this publication?
Marked list

Tools

Key

Free Content
Free content
New Content
New content
Open Access Content
Open access content
Subscribed Content
Subscribed content
Free Trial Content
Free trial content

Text size:

A | A | A | A
^ Back to top
Share this item with others: These icons link to social bookmarking sites where readers can share and discover new web pages. print icon Print this page