Targeting of ECM molecules and their metabolizing enzymes and receptors for the treatment of CNS diseases

TY - JOUR

T1 - Targeting of ECM molecules and their metabolizing enzymes and receptors for the treatment of CNS diseases

AU - Berezin, Vladimir

AU - Walmod, Peter Schledermann

AU - Filippov, Mikhail

AU - Dityatev, Alexander

PY - 2014

Y1 - 2014

N2 - Extracellular matrix (ECM) molecules, their receptors at the cell surface, and cell adhesion molecules (CAMs) involved in cell-cell or cell-ECM interactions are implicated in processes related to major diseases of the central nervous system including Alzheimer's disease (AD), epilepsy, schizophrenia, addiction, multiple sclerosis, Parkinson's disease, and cancer. There are multiple strategies for targeting the ECM molecules and their metabolizing enzymes and receptors with antibodies, peptides, glycosaminoglycans, and other natural and synthetic compounds. ECM-targeting treatments include chondroitinase ABC, heparin/heparan sulfate-mimicking oligosaccharides, ECM cross-linking antibodies, and drugs stimulating expression of ECM molecules. The amount or activity of ECM-degrading enzymes like matrix metalloproteinases can be modulated indirectly via the regulation of endogenous inhibitors like TIMPs and RECK or at the transcriptional and translational levels using, e.g., histone deacetylase inhibitors, synthetic inhibitors like Periostat, microRNA-interfering drugs like AC1MMYR2, and natural compounds like flavonoids, epigallocatechin-3-gallate, anacardic acid, and erythropoietin. Among drugs targeting the major ECM receptors, integrins, are the anticancer peptide cilengitide and anti-integrin antibodies, which have a potential for treatment of stroke, multiple sclerosis, and AD. The latter can be also potentially treated with modulators of CAMs, such as peptide mimetics derived from L1-CAM and NCAM1.

AB - Extracellular matrix (ECM) molecules, their receptors at the cell surface, and cell adhesion molecules (CAMs) involved in cell-cell or cell-ECM interactions are implicated in processes related to major diseases of the central nervous system including Alzheimer's disease (AD), epilepsy, schizophrenia, addiction, multiple sclerosis, Parkinson's disease, and cancer. There are multiple strategies for targeting the ECM molecules and their metabolizing enzymes and receptors with antibodies, peptides, glycosaminoglycans, and other natural and synthetic compounds. ECM-targeting treatments include chondroitinase ABC, heparin/heparan sulfate-mimicking oligosaccharides, ECM cross-linking antibodies, and drugs stimulating expression of ECM molecules. The amount or activity of ECM-degrading enzymes like matrix metalloproteinases can be modulated indirectly via the regulation of endogenous inhibitors like TIMPs and RECK or at the transcriptional and translational levels using, e.g., histone deacetylase inhibitors, synthetic inhibitors like Periostat, microRNA-interfering drugs like AC1MMYR2, and natural compounds like flavonoids, epigallocatechin-3-gallate, anacardic acid, and erythropoietin. Among drugs targeting the major ECM receptors, integrins, are the anticancer peptide cilengitide and anti-integrin antibodies, which have a potential for treatment of stroke, multiple sclerosis, and AD. The latter can be also potentially treated with modulators of CAMs, such as peptide mimetics derived from L1-CAM and NCAM1.

U2 - 10.1016/b978-0-444-63486-3.00015-3

DO - 10.1016/b978-0-444-63486-3.00015-3

M3 - Journal article

C2 - 25410365

SN - 0079-6123

VL - 214

SP - 353

EP - 388

JO - Progress in Brain Research

JF - Progress in Brain Research

ER -