3.1.2 Reduced expression of TJ and adhesion proteins
Decreased expression of TJ and adhesion proteins in spinal cords from
ALS patients has been confirmed using PCR and Western Blot. Henkelet al. assessed mRNA expression of zonula occludens-1, occludin,
and claudin-5 in lumbar spinal cord homogenates from individuals with
ALS (30 sporadic and 4 familial cases) and 16 non-ALS controls (Henkel,
Beers, Wen, Bowser & Appel, 2009). A significant reduction in zonula
occludens-1 and occludin levels were identified in sporadic ALS and
familial ALS, respectively, while claudin-5 was unchanged in both
sporadic and familial ALS. In another study, a significant decrease in
most TJ and adhesions proteins were reported in ALS spinal cord
(cervical and lumbar) relative to non-ALS controls, including zonula
occludens-1, occludin, claudin-5, JAM-1 and VE-cadherin (Garbuzova-Davis
et al., 2012). Despite decreased TJ protein expression at the ALS BSCB,
the junction morphology was generally well-preserved as assessed by
electron microscopy (Sasaki, 2015). Based on these TJ and adhesion
junction reductions, it would be predicted that spinal cord access of
molecules would be increased as a result of increased paracellular
permeability.