Affiliations: [a] State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, P.R. China | [b] State Key Laboratory of Analytical Chemistry for Life Science, Nanjing University, Nanjing, Jiangsu, P.R. China
Correspondence:
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Correspondence to: Dr. Lina Ji and Zichun Hua, Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, 22 Han Kou Road, 210093, P.R. China. Tel.: +86 25 83593692; Fax: +86 25 83324605; E-mails: [email protected]; [email protected].
Abstract: The presence of amyloid plaques and vascular amyloid deposits is one of the pathological features of Alzheimer's disease (AD). Amyloid plaques and vascular deposits mainly consist of amyloid-β (Aβ), which is a metabolic product of amyloid-β protein precursor cleaved by β- and γ-secretase. Soluble Aβ monomers readily aggregate into oligomers preceding the formation of insoluble fibrils, and Aβ oligomers are more toxic than fibrils. Intensive therapeutic efforts have been attempted in the treatment of AD targeting Aβ, including preventing Aβ generation, inhibiting Aβ aggregation, and promoting Aβ clearance. The results show that amyloid plaque burden is reduced together with improved cognition performance in AD. Gelsolin, a multifunctional actin-binding protein, exists intracellularly as a cytoplasmic form and extracellularly as a secreted form in blood/cerebrospinal fluid. Gelsolin is suggested to be implicated in AD, based on the findings that some changes of gelsolin are correlated with disease progression rate in AD patients. Gelsolin binds Aβ, inhibits its aggregation into fibrils, and protects cells from apoptosis induced by Aβ. More importantly, administration or overexpression of gelsolin results in significant reduction of amyloid load and decrease of Aβ level in AD transgenic mice. In this article, we review the most recent progress of gelsolin as a potential therapeutic strategy for treatment of AD, and discuss the possible mechanism involved in the clearance of amyloid plaques in AD.
