Table of Contents
Journal of Neurodegenerative Diseases
Volume 2017 (2017), Article ID 4810232, 13 pages
https://doi.org/10.1155/2017/4810232
Research Article

Disturbed Matrix Metalloproteinase Pathway in Both Age-Related Macular Degeneration and Alzheimer’s Disease

1Department of Genetics, UCL Institute of Ophthalmology, London, UK
2Nanobiotech Co., Ltd., Heungdeok IT Valley, Yongin, Republic of Korea
3Wolfson Centre for Age-Related Diseases, King’s College London, London, UK

Correspondence should be addressed to Ali Aijaz Hussain

Received 21 June 2016; Revised 12 October 2016; Accepted 17 November 2016; Published 18 January 2017

Academic Editor: Gal Bitan

Copyright © 2017 Ali Aijaz Hussain et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Purpose. Abnormal protein deposits including β-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 of β-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 (). 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.