Astaxanthin: A Marine Drug That Ameliorates Cerebrovascular-Damage-Associated Alzheimer’s Disease in a Zebrafish Model via the Inhibition of Matrix Metalloprotease-13

Abstract

Alzheimer’s disease (AD) is a major type of dementia disorder. Common cognitive changes occur as a result of cerebrovascular damage (CVD) via the disruption of matrix metalloproteinase-13 (MMP-13). In diabetic cases, the progress of vascular dementia is faster and the AD rate is higher. Patients with type 2 diabetes are known to have a higher risk of the factor for AD progression. Hence, this study is designed to investigate the role of astaxanthin (AST) in CVD-associated AD in zebrafish via the inhibition of MMP-13 activity. CVD was developed through the intraperitoneal and intracerebral injection of streptozotocin (STZ). The AST (10 and 20 mg/L), donepezil (1 mg/L), and MMP-13 inhibitor (i.e., CL-82198; 10 μM) were exposed for 21 consecutive days in CVD animals. The cognitive changes in zebrafish were evaluated through light and dark chamber tests, a color recognition test, and a T-maze test. The biomarkers of AD pathology were assessed via the estimation of the cerebral extravasation of Evans blue, tissue nitrite, amyloid beta-peptide aggregation, MMP-13 activity, and acetylcholinesterase activity. The results revealed that exposure to AST leads to ameliorative behavioral and biochemical changes. Hence, AST can be used for the management of AD due to its multi-targeted actions, including MMP-13 inhibition.

Immunomodulatory roles of metalloproteinases in rheumatoid arthritis

“…JNJ0966 can inhibit the activation of MMP9 zymogen and the subsequent generation of catalytically active enzymes ( Scannevin et al, 2017 ), while MMP-9-IN-1 binds to the hemopexin (PEX) domain of MMP-9 resulting in the abrogation of MMP-9 homodimerization and blockage of a downstream signaling pathway required for MMP-9-mediated cell migration ( Dufour et al, 2011 ). CL-82198 is a highly selective MMP13 inhibitor ( Paramakrishnan et al, 2023 ), which has been used to treat Alzheimer’s disease ( Paramakrishnan et al, 2023 ), liver fibrosis ( George et al, 2017 ), chronic periodontitis ( Hernandez Rios et al, 2009 ). However, the effect of these inhibitors on human arthritis is still in need of further investigation.…”