PMID- 31473329
OWN - NLM
STAT- MEDLINE
DCOM- 20210203
LR  - 20210203
IS  - 1873-1635 (Electronic)
IS  - 1350-9462 (Linking)
VI  - 74
DP  - 2020 Jan
TI  - Understanding the complexity of the matrix metalloproteinase system and its 
      relevance to age-related diseases: Age-related macular degeneration and 
      Alzheimer's disease.
PG  - 100775
LID - S1350-9462(19)30050-3 [pii]
LID - 10.1016/j.preteyeres.2019.100775 [doi]
AB  - Extracellular matrices (ECMs) are maintained by tightly coupled processes of 
      continuous synthesis and degradation. The degradative arm is mediated by a family 
      of proteolytic enzymes called the matrix metalloproteinases (MMPs). These enzymes 
      are released as latent proteins (pro-MMPs) and on activation are capable of 
      degrading most components of an ECM. Activity of these enzymes is checked by the 
      presence of tissue inhibitors of MMPs (TIMPs) and current opinion holds that the 
      ratio of TIMPs/MMPs determines the relative rate of degradation. Thus, elevated 
      ratios are thought to compromise degradation leading to the accumulation of 
      abnormal ECM material, whilst diminished ratios are thought to lead to excessive 
      ECM degradation (facilitating angiogenesis and the spread of cancer cells). Our 
      recent work has shown this system to be far more complex. MMP species tend to 
      undergo covalent modification leading to homo- and hetero-dimerization and 
      aggregation resulting in the formation of very large macromolecular weight MMP 
      complexes (LMMCs). In addition, the various MMP species also show a bound-free 
      compartmentalisation. The net result of these changes is to reduce the 
      availability of the latent forms of MMPs for the activation process. An 
      assessment of the degradation potential of the MMP system in any tissue must 
      therefore take into account the degree of sequestration of the latent MMP 
      species, a protocol that has not previously been addressed. Taking into 
      consideration the complexities already described, we will present an analysis of 
      the MMP system in two common neurodegenerative disorders, namely age-related 
      macular degeneration (AMD) and Alzheimer's disease (AD).
CI  - Copyright (c) 2019 Elsevier Ltd. All rights reserved.
FAU - Hussain, Ali A
AU  - Hussain AA
AD  - Department of Genetics, UCL Institute of Ophthalmology, London, UK. Electronic 
      address: alyhussain@aol.com.
FAU - Lee, Yunhee
AU  - Lee Y
AD  - Alt-Regen Co., Ltd, Heungdeok IT Valley, Yongin, Republic of Korea. Electronic 
      address: bestuni@gmail.com.
FAU - Marshall, John
AU  - Marshall J
AD  - Department of Genetics, UCL Institute of Ophthalmology, London, UK. Electronic 
      address: Eye.marshall@googlemail.com.
LA  - eng
GR  - DH_/Department of Health/United Kingdom
GR  - MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20190829
PL  - England
TA  - Prog Retin Eye Res
JT  - Progress in retinal and eye research
JID - 9431859
RN  - EC 3.4.24.- (Matrix Metalloproteinases)
SB  - IM
MH  - Aging/*metabolism
MH  - Alzheimer Disease/*enzymology
MH  - Extracellular Matrix/*metabolism
MH  - Humans
MH  - Macular Degeneration/*enzymology
MH  - Matrix Metalloproteinases/*metabolism
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - Extracellular matrix
OT  - Macular degeneration
OT  - Metalloproteinases
OT  - Protein aggregation
EDAT- 2019/09/02 06:00
MHDA- 2021/02/04 06:00
CRDT- 2019/09/02 06:00
PHST- 2019/06/27 00:00 [received]
PHST- 2019/08/25 00:00 [revised]
PHST- 2019/08/27 00:00 [accepted]
PHST- 2019/09/02 06:00 [pubmed]
PHST- 2021/02/04 06:00 [medline]
PHST- 2019/09/02 06:00 [entrez]
AID - S1350-9462(19)30050-3 [pii]
AID - 10.1016/j.preteyeres.2019.100775 [doi]
PST - ppublish
SO  - Prog Retin Eye Res. 2020 Jan;74:100775. doi: 10.1016/j.preteyeres.2019.100775. 
      Epub 2019 Aug 29.