Tissue transglutaminase: a novel therapeutic target in cerebral amyloid angiopathy.

Micha M M Wilhelmus, Mieke de Jager, Benjamin Drukarch

Department of Anatomy and Neurosciences, Neuroscience Campus Amsterdam, VU University Medical Center, Amsterdam, The Netherlands. m.wilhelmus@vumc.nl

Neuro-degenerative diseases 2012

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Accumulation of amyloid-β (Aβ) in brain vessel walls, known as cerebral amyloid angiopathy (CAA), plays a key role in Alzheimer's disease pathogenesis. CAA might result from impaired transport of Aβ out of the brain. Although the mechanisms underlying reduced Aβ transport are largely unknown, thickening of basement membrane extracellular matrix (ECM) is likely involved. Tissue transglutaminase (tTG) is an enzyme capable of modulating the ECM by covalently cross-linking ECM proteins. Recently, our group found that tTG and its cross-linking activity are associated with CAA pathology, suggesting a role for tTG in ECM modulation in CAA. Therefore, inhibition of tTG activity might be a promising novel therapeutic target to counteract CAA. Copyright © 2011 S. Karger AG, Basel.

Citation

Micha M M Wilhelmus, Mieke de Jager, Benjamin Drukarch. Tissue transglutaminase: a novel therapeutic target in cerebral amyloid angiopathy. Neuro-degenerative diseases. 2012;10(1-4):317-9