# Enhancement of the Neuroprotective Effect of
## 1 Introduction  
Dementia is a degenerative brain disease characterized by a decline in learning, and there is a considerable increase of social interest in its prevention and treatment [1]. In general, the mechanisms underlying the phenomena of the decline in memory and cognitive functions have been understood to be an excessive accumulation of amyloid \(\beta\) protein in the brain [2]. In additions to this, neurological degeneration resulting from nerve cell damage occurring during the decomposition of acetylcholine (ACh) by acetylcholinesterasen has also been considered to be a major mechanism that is associated with dementia [2,3]. Prolyl endopeptidase (PEP) is a protease that is known to be highly involved in the generation of amyloid \(\beta\) protein, and it digests proline, and it is one of key neuropeptides in the cerebral cortex of the brain [4,5]; therefore, PEP inhibitors have been developed as therapeutic agents to overcome declines in memory and cognitive function. In addition, severalchemicals that act as acetylcholinesterasecholinesteraseeras inhibitors, such as donepezil, rivastigmine, and galantamine, have also been developed to improve memory in dementia patients. However, these chemicals have demonstrated side effects such as hepatotoxicity, vomiting, diarrhea, and gastrointestinal disorders. Therefore, research has been actively conducted to develop therapeutic agents from natural resources to replace these medicines [6; 7; 8]. For this purpose, multiple studies have been conducted to develop health functional foods that help to improve cognitive function or memory impairment, such as Korean angelica roots, ginkgo leaves, and _Codonopsis lanccolata_[9; 10; 11]. The primary mechanism of these plants in enhancing cognitive function has been found to be their strong antioxidant activities, effectively inhibiting both oxidative stress and free radical generation [9; 10; 11]. However, no effective functional food that helps to improve cognitive function or memory impairment has been developed from marine resources. The marine microalgae _Spirulina maxima_, with a high antioxidant activity, has been shown to have various biological effects, including anticancer, anti-inflammatory, detoxification, and anti-cholesterol activities [12; 13]. These activities of _S. maxima_ stem from biologically active substances such as C-phycocyanin (C-PC), chlorophyll, carotenoid, novel sulfated polysaccharides, and vitamin B12 [14; 15; 16]. However, C-PC and chlorophyll, which are major bioactive components in _Spirulina_, have the disadvantage of being easily broken down by light and high temperatures during conventional processing [17; 18]. Most conventional methods of processing _S. maxima_ would inevitably be affected by physical factors such as exposure to sunlight, oxygen, and high temperatures [19]. In addition to these difficulties, the utilization of the fermentation process has not been employed to process _S. maxima_, and except for kelp, fermentation has seldom been used for marine microalgae, even though lactic acid fermentation has been widely employed to develop other functional food materials [20]. Among bacteria, the lactic acid bacterium has been the most commonly used for the fermentation of functional foods. In general, the fermentation process has been proven to increase the biological activity of this bacteria, including its anticancer, immunological enhancement, and antibacterial activities. Recent studies have also reported that lactic acid bacteria have antioxidant and whitening effects [21]. _S. maxima_ has been fermented by lactic acid bacteria isolated from fermented vegetables (i.e., kimchi) (MG547899, National Center for Biotechnology Information, GenBank, USA) in an effort to derive greater memory improvement effects [21]. To ensure the enhancement of its biological activities, in the current study, the fermentation of _S.