Parkinson's disease is the second most common neurodegenerative disease after Alzheimer's disease. The reporter recently learned that the team led by Yu Jintai from the National Center for Neurological Diseases, the National Key Laboratory of Brain Function and Brain Diseases, and the Huashan Hospital affiliated with Fudan University, after 5 years of clinical and basic research, has made significant scientific breakthroughs and discovered a new therapeutic target FAM171A2 protein for Parkinson's disease, as well as small molecule compounds with potential therapeutic effects. This breakthrough is expected to intervene in Parkinson's disease from the early stages and delay disease progression. By combining existing targeted treatment methods, a dual breakthrough in the treatment of Parkinson's disease etiology and symptom relief will be achieved, benefiting millions of patients. The relevant research results were recently published online in the international journal Science. Previous studies have found that pathological alpha synuclein is a key pathogenic protein in Parkinson's disease. Under pathological conditions, normal alpha synuclein monomers undergo misfolding and aggregate to form fibers, disrupting the normal function of neurons and leading to their death. It will also spread like a 'seed', invading neighboring normal neurons, inducing more brain area alpha synuclein aggregation and neuronal death. When pathogenic proteins spread to the substantia nigra of the midbrain, they can cause the death of dopaminergic neurons, resulting in motor symptoms such as bradykinesia, resting tremor, and muscle rigidity; When it spreads to the cerebral cortex, cognitive impairment symptoms such as memory loss may occur. Traditional medicine and surgical treatment only target the symptoms of Parkinson's disease and cannot delay disease progression. Therefore, further research on the underlying causes of Parkinson's disease and targeted treatment has become a goal that scientists in related fields around the world are competing to explore. After 5 years of dedicated research, the Yu Jintai team has identified the "trigger" for the transmission of pathological alpha synuclein between neurons, and discovered candidate new drugs that inhibit its transmission process, providing new ideas for the treatment of Parkinson's disease. The research team first identified FAM171A2 protein as a Parkinson's disease risk gene through genome-wide association analysis of a large population. FAM171A2 protein is a neuronal cell membrane protein, but its function has never been studied before. The team's research has confirmed that FAM171A2 protein is the key to promoting the spread of pathological alpha synuclein. Our scientists have revealed for the first time in the world the binding mechanism between FAM171A2 protein and alpha synuclein. Based on clinical sample analysis of Parkinson's disease patients, the team found that the FAM171A2 protein content in the brain of Parkinson's disease patients is increased, and the higher the FAM171A2 protein content, the higher the pathological alpha synuclein content in the brain. Subsequently, through a series of in vitro and in vivo experiments, the team found that on the neuronal cell membrane, FAM171A2 protein, like an "intelligent recognition gate," can selectively bind to pathological alpha synuclein and carry it into neurons, inducing misfolding of monomeric alpha synuclein within neurons, resulting in neuronal death and propagation between neurons. Subsequently, it was confirmed through transgenic animals that knocking out the FAM171A2 protein on mouse neurons can effectively control the progression of Parkinson's like symptoms in mice. Based on this discovery, the team utilized artificial intelligence's protein structure prediction and virtual screening techniques to successfully identify a small molecule from over 7000 small molecule compounds that can effectively inhibit the binding of FAM171A2 protein to pathological alpha synuclein and suppress the uptake of the pathogenic protein fibers by dopaminergic neurons. Yu Jintai told reporters that Parkinson's disease patients already have alpha synuclein pathology in their brains more than a decade before the onset of motor symptoms. This study is expected to block the spread of pathological alpha synuclein and delay the progression of Parkinson's disease by targeting and inhibiting the original new target FAM171A2 protein in the preclinical, prodromal, and clinical stages of the disease. (New Society)