Molecular Cobalt(II) Complexes for Tau Polymerization in Alzheimer’s Disease

Autor:	Pramod G. Nagaraju, Subashchandrabose Chinnathambi, Vinod G. Landge, Poornima Priyadarshini Cg, Ekambaram Balaraman, Nalini Vijay Gorantla
Rok vydání:	2019
Předmět:	biology General Chemical Engineering chemistry.chemical_element Hyperphosphorylation General Chemistry Fibril Article Contemporary science Chemistry Tubulin Dual role chemistry Polymerization mental disorders biology.protein Biophysics QD1-999 Cobalt
Zdroj:	ACS Omega, Vol 4, Iss 16, Pp 16702-16714 (2019) ACS Omega
ISSN:	2470-1343
Popis:	Tau is an axonal protein known to form abnormal aggregates and is the biomarker of Alzheimer's disease. Metal-based therapeutics for inhibition of Tau aggregation is limited and rarely reported in contemporary science. Here, we report the first example of rationally designed molecular cobalt(II)-complexes for effective inhibition of Tau and disaggregation of preformed Tau fibrils. The mechanistic studies reveal that prevention of Tau aggregation by cobalt-based metal complexes (CBMCs) is concentration-dependent and Tau seldom exhibits conformational changes. Interestingly, CBMCs play dual role in causing disassembly of preformed aggregates as well as inhibition of complete Tau aggregation. Furthermore, CBMCs were nontoxic and maintained the tubulin network intact. CBMCs also prevented okadaic acid-induced toxicity in SH-SY5Y cells thus, preventing hyperphosphorylation of Tau. We believe that this unprecedented finding by the newly developed molecular complexes has a potential toward metal-based therapeutics for Alzheimer's disease.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::54d09e02ecf1a9886bbfba855e9c96e2 https://doi.org/10.1021/acsomega.9b00692 Zobrazit plný text záznamu