title: Disturbed Matrix Metalloproteinase Pathway in Both Age-Related Macular Degeneration and Alzheimer's Disease.
abstract: Purpose.Abnormal protein deposits includingβ-amyloid, found in ageing Bruch's membrane and brain, are susceptible to degradation by matrix metalloproteinases (MMPs). In ageing Bruch's membrane, these MMPs become less effective due to polymerisation and aggregation reactions (constituting the MMP Pathway), a situation much advanced in age-related macular degeneration (AMD). The likely presence of this MMP Pathway in brain with the potential to compromise the degradation ofβ-amyloid associated with Alzheimer's disease (AD) has been investigated.Methods.Presence of high molecular weight MMP species (HMW1 and HMW2) together with the much larger aggregate termed LMMC was determined by standard zymographic techniques. Centrigugation and gel filtration techniques were used to separate and quantify the distribution between bound and free MMP species.Results.The MMP Pathway, initially identified in Bruch's membrane, was also present in brain tissue. The various MMP species displayed bound-free equilibrium and in AD samples, the amount of bound HMW1 and pro-MMP9 species was significantly reduced (p< 0.05). The abnormal operation of the MMP Pathway in AD served to reduce the degradation potential of the MMP system.Conclusion.The presence and abnormalities of the MMP Pathway in both brain and ocular tissues may therefore contribute to the anomalous deposits associated with AD and AMD.
authors.affiliation: Department of Genetics, UCL Institute of Ophthalmology, London, UK.
authors.forename: Ali Aijaz
authors.identifier: 0000-0003-0388-4908
authors.initials: AA
authors.lastname: Hussain
authors.affiliation: Nanobiotech Co., Ltd., Heungdeok IT Valley, Yongin, Republic of Korea.
authors.forename: Yunhee
authors.initials: Y
authors.lastname: Lee
authors.affiliation: Department of Genetics, UCL Institute of Ophthalmology, London, UK.
authors.forename: Jin-Jun
authors.initials: JJ
authors.lastname: Zhang
authors.affiliation: Wolfson Centre for Age-Related Diseases, King's College London, London, UK.
authors.forename: Paul T
authors.initials: PT
authors.lastname: Francis
authors.affiliation: Department of Genetics, UCL Institute of Ophthalmology, London, UK.
authors.forename: John
authors.identifier: 0000-0001-6372-9294
authors.initials: J
authors.lastname: Marshall