TABLE 1.

Analysis of several CNS pathologies and their impact in tissue structure.

Disorder	Tissue stiffness	ECM remodeling	Signaling pathway involved	Possible therapeutic target	References
Retinal Detachment	↓	Yes	Hippo EGFR Notch	RPE pumps	Sivak and Fini, 2002; Morante and Desplan, 2004; Dupont et al., 2011; Chou and Siegel, 2012;
Glaucoma	↑	Yes	Hippo	Optic nerve head mechanics	Rosario Hernandez and Pena, 1997; Heijl et al., 2002; Kass et al., 2002; Dupont et al., 2011
Migraine	=	Yes (mild)	PKC MMP activity	CNS-blood vessels crosstalk	Goadsby et al., 1990; Di Castro et al., 2006; Martins-Oliveira et al., 2009; Nassini et al., 2010; Lakhan and Avramut, 2012
CNS injury	↓	Yes	PKC Rho/ROCK MAP kinase	BBB permeability	Krizbai and Deli, 2003
	↓	Yes	EGFR Rho/ROCK	Glia architecture	Morante and Desplan, 2004
	↓	Yes	ERK PKC	MMP activity	Hsieh et al., 2010
	↓	Yes	Rho/ROCK PKC	CSPGs	Morgenstern et al., 2002
Alzheimer’s	↓	Yes	Rho/ROCK PLA2	Aβ fibrils	Moses et al., 2006
	↓	Yes	Rho-ROCK	ROCK	Jagielska et al., 2012; Hensel et al., 2015
	↓	Yes	ERK PKC	MMP activity	Hsieh et al., 2010
Parkinson	↓	Yes	Rho/ROCK pathway	ROCK	Jagielska et al., 2012; Hensel et al., 2015
	↓	Yes	ERK PKC	MMP activity	Hsieh et al., 2010
Multiple Sclerosis	↓	Yes	Rho-ROCK	ROCK	Jagielska et al., 2012; Hensel et al., 2015
	↓	Yes	ERK PKC	MMP activity	Hsieh et al., 2010
Cancer	↑	Yes	FAK signaling Rho/ROCK signaling	Talin-1 MMP activity	Ulrich et al., 2009; Sen et al., 2012

↑, increased stiffness; ↓, decreased stiffness; =, unchanged stiffness; EGFR, Epidermal growth factor receptor; RPE, retinal pigment epithelium; PKC, protein kinase C; CNS, central nervous system; ROCK, Rho-associated protein kinase; BBB, brain blood barrier; ERK, extracellular signal–regulated kinase; MMP, matrix metalloproteinase; CSPG, chondroitin sulfate proteoglycan; PLA₂, Phospholipase A2; FAK, Focal adhesion kinase.