An in-silico approach: identification of PPAR-γ agonists from seaweeds for the management of Alzheimer’s Disease

Abstract

Alzheimer’s Disease is a complex progressive neurodegenerative disorder characterized by neurofibrillary tangles and senile plaques in various parts of the brain particularly cerebral cortex affecting memory and cognition. Nuclear receptors such as Peroxisome proliferator-activated receptor γ [PPAR-γ] is reported to have a role in lipid and glucose homeostasis in the brain, reduces the synthesis of Aβ (beta-amyloid plaques) and also regulates mitochondrial biogenesis and inhibit the neuro-inflammation, which contributes for the improvement in the cognitive function in AD. Hence PPAR-γ is one of the newer targets for the researchers to understand the pathology of AD and to evolve the novel strategy to retard/reverse the progression of AD. PPAR-γ agonists such as Rosiglitazone and Pioglitazone have shown promising results in AD by decreasing neuro-inflammation and restoring glucose dysmetabolism leading to a reduction in neuronal deterioration. These agonists possess poor blood-brain permeability and are poor candidates for clinical use in AD. Therefore, search, design, and development for new PPAR- γ agonists with improved BBB penetration ability are imperative. The present work deals with the use of computational tools and techniques such as molecular docking, molecular dynamics to discover PPAR-γ agonists from the unexplored Seaweed Metabolite Database and predicts it’s toxicological and physiochemical profile, thereby saving time and resources. Out of 1,110 seaweed compounds, the hit molecule BS052 displayed a strong binding affinity towards PPAR-γ, which possessed better lipid solubility indicating the potential to be considered as a PPAR-γ agonist, which may be useful in the management of AD.

Communicated by Ramaswamy H. Sarma.

Graphical Abstract

Keywords:

• Alzheimer’s Disease
• PPAR-γ
• molecular docking
• molecular dynamics
• ADME
• MM-GBSA

Acknowledgment

The authors are acknowledging the support and facilities provided by the Government College of Pharmacy, Bengaluru.

Disclosure statement

No potential conflict of interest was reported by the author(s).