Alzheimer's disease (AD) is a chronic and devastating neurodegenerative disorder that is affecting elderly people at an increasing rate. Clusterin (CLU), an extracellular chaperone, is an ubiquitously expressed protein that can be identified in various body fluids and tissues. Expression of CLU can lead to various processes including suppression of complement system, lipid transport, chaperone function, and also controlling neuronal cell death and cell survival mechanisms. Studies have confirmed that the level of CLU expression is increased in AD. Furthermore, CLU also decreased the toxicity and aggregation of amyloid beta (Aβ). However when the Aβ level was far greater than CLU, then the amyloid generation was increased. CLU was also found to incorporate in the amyloid aggregates, which were more harmful as compared with the Aβ42 aggregates alone. Growing evidence indicates that CLU plays roles in AD pathogenesis via various processes, including aggregation and clearance of Aβ, neuroinflammation, lipid metabolism, Wnt signaling, copper homeostasis, and regulation of neuronal cell cycle and apoptosis. In this article, we represent the critical interaction of CLU and AD based on recent advances. Furthermore, we have also focused on the Aβ-dependent and Aβ-independent mechanisms by which CLU plays a role in AD pathogenesis.
Keywords: APOJ; Alzheimer’s disease; Amyloid beta; Clusterin; Neuroinflammation; Wnt signaling.
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