Understanding the complexity of the matrix metalloproteinase system and its relevance to age-related diseases: Age-related macular degeneration and Alzheimer's disease

Publication date: Available online 29 August 2019Source: Progress in Retinal and Eye ResearchAuthor(s): Ali A. Hussain, Yunhee Lee, John MarshallAbstractExtracellular 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 a...
Source: Progress in Retinal and Eye Research - Category: Opthalmology Source Type: research