
 
                Major
                    Depressive Disorder
                    
(MDD)
                (MDD)
                    is a severe mental health conditions
                    characterized by persistent feelings of
                    sadness, loss of interest in activities, and
                    various emotional and physical problems.
                
             
                Globally,
                    approximately 280 million people suffer from
                    depression, accounting for 3.8% of the total population.
                
                    In China,about 95 million people are affected by
                    depression,with around
                    280,000 committing suicide
                    each year, 40% of whom
                    have severe depression.
                
            In recent
                    years, the prevalence of depression among
                    adolescents has significantly increased, reaching
                
                15-20%
                
            
                    However,
                    antidepressant medications currently face issues
                    such as significant side effects, drug resistance, delayed
                    efficacy, and heavy economic burdens on patients, all of which
                    affect patient compliance and therapeutic outcomes.
             
                     
                        
                            Literature showed that the
                            decoupling of SERT-nNOS can
                            effectively enhance the activation of
                            serotonergic neuronsin DRN
                            exerting rapid antidepressant effects.
                        
                    
                Utilizing molecular docking and SPR, we identified inosine as a
                molecule capable of successfully decoupling SERT-nNOS
            
             
                    
                    We engineered Lactobacillus plantarum L168 to
                    produce inosine by incorporating the key enzyme
                    seauence asK
                
            
                Upon administration, the engineered probiotics reach the gut and
                release inosine, which then enters the brain through blood
                circulation and the gut-brain axis, effectively disconnecting SERT
                from nNOS to alleviate depressive symptoms.
            
            
             
                 
                
                Accordingly, we genetically engineered Lactobacillus plantarum L168 to biosynthesize theanine and
                niacin, aiming to develop therapy for Alzheimer's disease and depressions, respectively. Our aim is to
                assist patients suffering from depression and Alzheimer's Disease in reclaiming their cognitive
                functions and emotional well-being.
            
         
        

 
                                 
                                     
                                 
                                 
                                 
                         
                         
                         
                         
                         
                         
                         
                        