Affiliations: [a] Neuroinflammation Group, Faculty of Medicine and Health Sciences, Macquarie University, NSW, Australia
| [b] Centre for Healthy Brain Ageing, School of Psychiatry, University of New South Wales, Faculty of Medicine, Sydney, Australia
Correspondence:
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Correspondence to: Prof. Gilles Guillemin, Neuroinflammation Group, Faculty of Medicine and Health Sciences, Macquarie University, NSW, Australia. Tel.: +61 2 9350 2727; E-mail: [email protected].
Abstract: Background:The accumulation of extracellular plaques containing amyloid-β protein (Aβ) in the brain is one of the main pathological hallmarks of Alzheimer’s disease (AD). Aβ peptide can promote the production of highly volatile free radicals and reactive oxygen species (ROS) that can induce oxidative damage to neurons and astrocytes. At present, numerous studies have investigated the neuroprotective and glioprotective effects of natural products derived from plants, animals, and microorganisms. Objective:We investigated the glioprotective effect of secondary metabolites obtained from Herpetosiphon sp. HM 1988 against Aβ40-induced toxicity in human primary astrocytes. Methods:The protective effect of bacterial secondary metabolites against Aβ40-induced inducible nitric oxide synthase (iNOS) activity was evaluated using the citrulline assay. To confirm the iNOS activity, nitrite production was assessed using the fluorometric Griess diazotization assay. Intracellular NAD+ depletion and lactate dehydrogenase (LDH) release in human primary astrocytes were also examined using well-established spectrophotometric assays. Results:Our results indicate that Aβ40 can induce elevation in iNOS and LDH activities, nitrite production, and cellular energy depletion. Importantly, extract of Herpetosiphon sp. HM 1988 decreased iNOS activity, nitrite production, and LDH release. In addition, metabolites of the strain were able to restore cellular energy deficits through inhibition of NAD+ depletion mediated by Aβ40. Conclusion:These findings suggest that Herpetosiphon metabolites may represent a promising, novel source for the prevention of Aβ toxicity in AD.
