The Dynamics of CD147 in Alzheimer's Disease Development and Pathology

Article type: Review Article

Authors: Kanyenda, Limbikani J.^a | Verdile, Giuseppe^{a; b; c} | Boulos, Sherif^c | Krishnaswamy, Sudarsan^a | Taddei, Kevin^{a; b; c} | Meloni, Bruno P.^{c; d} | Mastaglia, Frank L.^c | Martins, Ralph N.^{a; b; c; *}

Affiliations: [a] Centre of Excellence for Alzheimer's Disease Research and Care, School of Exercise, Biomedical and Health Sciences, Edith Cowan University, Joondalup, WA, Australia | [b] McCusker Foundation for Alzheimer's Disease Research, Hollywood Private Hospital, Nedlands, WA, Australia | [c] Centre for Neuromuscular and Neurological Disorders, University of Western Australia, Crawley Australia | [d] Department of Neurosurgery, Sir Charles Gairdner Hospital, Nedlands, WA, Australia

Correspondence: [*] Correspondence to: Ralph N. Martins, Edith Cowan University, Centre of Excellence for Alzheimer's Research and Care, 100 Joondalup Drive, WA 6027. Tel.: +61 8-63045456; Fax: +61 8 63045851; E-mail: r.martins@ecu.edu.au.

Abstract: CD147, also known as basigin, EMMPRIN, neurothelin, TCSF, M6, HT7, OX47, or gp42, is a transmembrane glycoprotein of the immunoglobulin super-family. It is expressed in many neuronal and non-neuronal tissues including the hippocampus, pre-frontal cortex thyroid, heart, early erythroid, amygdala, and placenta. This protein is involved in various cellular and biological functions, such as lymphocyte migration and maturation, tissue repair cancer progression, T and B lymphocyte activation, and induction of extracellular matrix metalloproteinase. The CD147 protein interacts with other proteins such as cyclophilin A (CyPA), Cyclophilin B (CyPB), sterol carrier protein (SCP), caveolin-1 and integrins, and can influence amyloid-β (Aβ) peptide levels, a protein that is central to Alzheimer's disease (AD) pathogenesis. Mechanisms by which CD147 regulate Aβ levels remain unclear, thus in this review we discuss its involvement in Aβ production and clearance and potential mechanisms by which controlling CD147 levels could impact on Aβ accumulation and AD pathogenesis.

Keywords: Alzheimer's disease, amyloid-β, amyloid-β protein precursor, CD147, cholesterol, EMMPRIN, γ-secretase, immunoglobulin superfamily, sterol carrier protein-2

DOI: 10.3233/JAD-2011-110584

Journal: Journal of Alzheimer's Disease, vol. 26, no. 4, pp. 593-605, 2011