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Parkinson\u2019s disease (PD) is a progressive neurodegenerative disease characterized by degeneration of dopaminergic neurons and motor dysfunction. This study utilized bioinformatics and network pharmacology methods to predict the anti-PD mechanism of ALC and established in vivo and in vitro PD models using 6-hydroxydopamine (6-OHDA) for experimental verification. Network pharmacological analysis indicates that apoptosis regulation and the PKA\/p-CREB\/BDNF signaling pathway are closely related to the anti-PD effect of ALC, and protein kinase A (PKA) and dopamine transporter (DAT) are key molecular targets. The experimental results show that ALC administration can alleviate the cytotoxicity of SH-SY5Y induced by 6-OHDA and simultaneously improve the motor dysfunction and dopaminergic neuron loss in PD mice. In addition, ALC can also activate the PKA\/p-CREB\/BDNF signaling pathway and increase the DAT level in brain tissue, regulate the expression of BAX and Bcl-2, and reduce neuronal apoptosis. These results indicate that ALC can exert anti-PD effects by up-regulating the PKA\/p-CREB\/BDNF\/DAT signaling pathway and inhibiting neuronal apoptosis, providing theoretical support for the application of ALC in PD.<\/jats:p>","DOI":"10.3390\/molecules30153265","type":"journal-article","created":{"date-parts":[[2025,8,4]],"date-time":"2025-08-04T15:30:06Z","timestamp":1754321406000},"page":"3265","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Garlic-Derived Allicin Attenuates Parkinson\u2019s Disease via PKA\/p-CREB\/BDNF\/DAT Pathway Activation and Apoptotic Inhibition"],"prefix":"10.3390","volume":"30","author":[{"given":"Wanchen","family":"Zeng","sequence":"first","affiliation":[{"name":"School of Medicine, Guangxi University, Nanning 530004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingkai","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Medicine, Guangxi University, Nanning 530004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Medicine, Guangxi University, Nanning 530004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaomin","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Medicine, Guangxi University, Nanning 530004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongquan","family":"Qi","sequence":"additional","affiliation":[{"name":"School of Medicine, Guangxi University, Nanning 530004, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e464","DOI":"10.1016\/S2666-7568(24)00094-1","article-title":"Temporal Trends in the Prevalence of Parkinson\u2019s Disease from 1980 to 2023: A Systematic Review and Meta-Analysis","volume":"5","author":"Zhu","year":"2024","journal-title":"Lancet Healthy Longev."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"101834","DOI":"10.1016\/j.arr.2022.101834","article-title":"Premotor, Nonmotor and Motor Symptoms of Parkinson\u2019s Disease: A New Clinical State of the Art","volume":"84","author":"Sallem","year":"2023","journal-title":"Ageing Res. 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