Seaweed Secondary Metabolites as a therapeutic approach for Alzheimer's disease: In Silico Approach

Abstract

Alzheimer’s disease (AD) is the most common type of dementia, presenting significant and escalating global challenges. AD is a progressive neurodegenerative disorder characterized by the cognitive decline, memory loss, and impaired daily functioning. The pathology of AD is characterized by the accumulation of amyloid beta aggregates and hyperphosphorylated tau protein tangles in the brain, along with neuroinflammation, impaired synaptic function and cholinergic dysfunction. Current pharmacological interventions such as donepezil, rivastigmine, and galantamine provide only symptomatic relief and are often associated with adverse effects, underscoring the need for alternative therapeutics. The present study employs an in silico approach to identify potential anti-Alzheimer’s candidates among secondary metabolites derived from seaweeds. A total of 1072 compounds from the Seaweed Metabolite Database (SWMD) were screened against key AD-associated targets acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and beta-amyloid peptides. Protein structures were refined and validated using RAMPAGE, and active binding sites were predicted using CASTp. Molecular docking using PyRx revealed several potent interactions, with BB002, RR010, RR035, and GC601 exhibiting strong binding affinities and stable hydrogen bond formation within the active sites. ADMET profiling confirmed favorable pharmacokinetic parameters and non-toxic properties of these compounds. These findings suggest that specific seaweed-derived secondary metabolites exhibit significant potential to modulate cholinesterase activity and amyloid aggregation, highlighting their promise as natural leads for the development of neuroprotective therapeutics against AD.