TY  - JOUR
AU  - Ulbrich, Philipp
AU  - Khoshneviszadeh, Mashima
AU  - Jandke, Solveig
AU  - Schreiber, Stefanie
AU  - Dityatev, Alexander
TI  - Interplay between perivascular and perineuronal extracellular matrix remodelling in neurological and psychiatric diseases.
JO  - European journal of neuroscience
VL  - 53
IS  - 12
SN  - 1460-9568
CY  - Oxford [u.a.]
PB  - Wiley
M1  - DZNE-2021-00148
SP  - 3811-3830
PY  - 2021
N1  - ISSN 1460-9568 not unique: **3 hits**.
AB  - Vascular damage, central nervous system (CNS) injury, seizure or even psychological stress may trigger activation of microglia and infiltration of other immune cells, accompanied by high levels of expression and activity of extracellular proteases, such as matrix metalloproteinases (MMPs), and degradation/remodelling of the perivascular and perineuronal extracellular matrix (ECM). This acute response is followed by the recovery/chronic phase, during which the activation of astrocytes leads to the upregulated synthesis of ECM molecules, which, in combination with elevated expression of tissue inhibitor of metalloproteinases (TIMP) proteins, increases the aggregation of ECM molecules. This biphasic dysregulation of local balance between extracellular proteases and the ECM activates multiple temporally overlapping signalling cascades, involving receptor-type protein tyrosine phosphatases, integrins, Toll-like receptors, cell adhesion molecules, and ion channels, resulting in impaired synaptic plasticity and cognition. An additional level of complexity is related to the leakage of blood plasma proteins, such as fibrinogen, and the diffusion of perivascularly overproduced MMPs, TIMPs and ECM molecules into the CNS parenchyma, leading to diverse effects on neurons and incorporation of these molecules into the interstitial neural ECM. This review aims to outline these complex common mechanisms in stroke, CNS injury, depression, epilepsy, multiple sclerosis and cerebral small vessel disease and to discuss translational strategies to advance the development of new therapies for these neurological and psychiatric diseases.
KW  - Astrocytes
KW  - Extracellular Matrix
KW  - Humans
KW  - Matrix Metalloproteinases
KW  - Mental Disorders
KW  - Nervous System Diseases
KW  - Neurons
KW  - Tissue Inhibitor of Metalloproteinases
KW  - cerebral small vessel disease (Other)
KW  - perineuronal extracellular matrix (Other)
KW  - perivascular extracellular matrix (Other)
KW  - stroke (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:32594588
DO  - DOI:10.1111/ejn.14887
UR  - https://pub.dzne.de/record/154294
ER  -